Melanoma

CHICAGO — Topical therapy for 2 or 3 days with the investigational agent ingenol mebutate, also known as PEP005, provides substantial clearance of actinic keratosis lesions, according to findings from two phase II randomized studies.

"A comparison of efficacy outcomes with those of studies of diclofenac, 5-FU [fluorouracil], and imiquimod shows at least equivalent clearance of lesions over a much shorter period," Dr. Lawrence Anderson, one of the current study's lead investigators, reported at the American Academy of Dermatology's Academy 2008 meeting.

Ingenol mebutate gel has the potential to enhance compliance not only by its shorter course of therapy, but also by the truncated period of irritation in patients with actinic keratosis (AK), the investigators suggested.

PEP005 is a new class of compound derived from the sap of Euphorbia peplus, a readily available plant that has been used in Australia for centuries as a traditional treatment for skin conditions. The two current studies were sponsored by Peplin Ltd. of Brisbane, Australia, which is developing PEP005.

Dr. Anderson, who is in private dermatology practice in Tyler, Texas, and his associates randomized 222 patients with 4- 8 visible AK lesions on the arm, shoulder, chest, back, or scalp, to one of four treatment groups. The primary end point was partial clearance, defined as the proportion of patients at day 57 with 75% reduction in the number of AK lesions identified at baseline.

Treatment with PEP005 gel once daily for 2 or 3 days produced significantly greater lesion clearance in a dose-dependent manner by all measures and at all dosing regimens, compared with a control vehicle applied once daily for 3 days.

The partial clearance rate was 22% for vehicle, 56% for ingenol mebutate gel 0.025% for 3 days, 62% for ingenol mebutate gel 0.05% for 2 days, and 75.4% for ingenol mebutate 0.05% for 3 days.

The proportion of patients at day 57 with complete clearance, defined as no clinically visible AK lesions, was 12%, 40%, 44%, and 54.4%, respectively.

All three active treatments were well tolerated, according to the investigators, one of whom was a Peplin employee. The most common lesion-site reactions on day 57 were erythema, experienced by 34% of 162 actively treated patients; flaking or scaling (29%); and crusting (9%).

Because AK lesions on the trunk and extremities historically are more difficult to treat than scalp lesions, the investigators performed an ad hoc analysis to compare outcomes in patients with scalp and nonscalp lesions, Dr. Michael Freeman of the Skin Centre, Gold Coast, Australia, and his associates said in a separate poster.

Overall, scalp treatment areas had a higher complete clearance rate than nonscalp treatment areas (57% vs. 42.4%), although the gel was better tolerated when applied to nonscalp areas, regardless of concentration or dosing schedule, the investigators wrote.

The maximum tolerated dose (MTD) for face or face and scalp AK was determined to be once-daily ingenol mebutate gel 0.025% for 2 days, according to a second study that evaluated six formulation strengths ranging from 0.0025% to 0.025% in 86 patients with lesions limited to the face or face and scalp.

At the MTD, 26 of 36 patients (72%) achieved partial clearance and 14 of the 36 (39%) achieved complete clearance.

Ingenol mebutate gel was well tolerated across all strengths, with erythema the most common lesion site reaction. Three patients experienced four serious adverse events, none considered treatment related, according to the investigators, one of whom was also a Peplin employee.

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CHICAGO — Topical therapy for 2 or 3 days with the investigational agent ingenol mebutate, also known as PEP005, provides substantial clearance of actinic keratosis lesions, according to findings from two phase II randomized studies.

"A comparison of efficacy outcomes with those of studies of diclofenac, 5-FU [fluorouracil], and imiquimod shows at least equivalent clearance of lesions over a much shorter period," Dr. Lawrence Anderson, one of the current study's lead investigators, reported at the American Academy of Dermatology's Academy 2008 meeting.

Ingenol mebutate gel has the potential to enhance compliance not only by its shorter course of therapy, but also by the truncated period of irritation in patients with actinic keratosis (AK), the investigators suggested.

PEP005 is a new class of compound derived from the sap of Euphorbia peplus, a readily available plant that has been used in Australia for centuries as a traditional treatment for skin conditions. The two current studies were sponsored by Peplin Ltd. of Brisbane, Australia, which is developing PEP005.

Dr. Anderson, who is in private dermatology practice in Tyler, Texas, and his associates randomized 222 patients with 4- 8 visible AK lesions on the arm, shoulder, chest, back, or scalp, to one of four treatment groups. The primary end point was partial clearance, defined as the proportion of patients at day 57 with 75% reduction in the number of AK lesions identified at baseline.

Treatment with PEP005 gel once daily for 2 or 3 days produced significantly greater lesion clearance in a dose-dependent manner by all measures and at all dosing regimens, compared with a control vehicle applied once daily for 3 days.

The partial clearance rate was 22% for vehicle, 56% for ingenol mebutate gel 0.025% for 3 days, 62% for ingenol mebutate gel 0.05% for 2 days, and 75.4% for ingenol mebutate 0.05% for 3 days.

The proportion of patients at day 57 with complete clearance, defined as no clinically visible AK lesions, was 12%, 40%, 44%, and 54.4%, respectively.

All three active treatments were well tolerated, according to the investigators, one of whom was a Peplin employee. The most common lesion-site reactions on day 57 were erythema, experienced by 34% of 162 actively treated patients; flaking or scaling (29%); and crusting (9%).

Because AK lesions on the trunk and extremities historically are more difficult to treat than scalp lesions, the investigators performed an ad hoc analysis to compare outcomes in patients with scalp and nonscalp lesions, Dr. Michael Freeman of the Skin Centre, Gold Coast, Australia, and his associates said in a separate poster.

Overall, scalp treatment areas had a higher complete clearance rate than nonscalp treatment areas (57% vs. 42.4%), although the gel was better tolerated when applied to nonscalp areas, regardless of concentration or dosing schedule, the investigators wrote.

The maximum tolerated dose (MTD) for face or face and scalp AK was determined to be once-daily ingenol mebutate gel 0.025% for 2 days, according to a second study that evaluated six formulation strengths ranging from 0.0025% to 0.025% in 86 patients with lesions limited to the face or face and scalp.

At the MTD, 26 of 36 patients (72%) achieved partial clearance and 14 of the 36 (39%) achieved complete clearance.

Ingenol mebutate gel was well tolerated across all strengths, with erythema the most common lesion site reaction. Three patients experienced four serious adverse events, none considered treatment related, according to the investigators, one of whom was also a Peplin employee.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Topical therapy for 2 or 3 days with the investigational agent ingenol mebutate, also known as PEP005, provides substantial clearance of actinic keratosis lesions, according to findings from two phase II randomized studies.

"A comparison of efficacy outcomes with those of studies of diclofenac, 5-FU [fluorouracil], and imiquimod shows at least equivalent clearance of lesions over a much shorter period," Dr. Lawrence Anderson, one of the current study's lead investigators, reported at the American Academy of Dermatology's Academy 2008 meeting.

Ingenol mebutate gel has the potential to enhance compliance not only by its shorter course of therapy, but also by the truncated period of irritation in patients with actinic keratosis (AK), the investigators suggested.

PEP005 is a new class of compound derived from the sap of Euphorbia peplus, a readily available plant that has been used in Australia for centuries as a traditional treatment for skin conditions. The two current studies were sponsored by Peplin Ltd. of Brisbane, Australia, which is developing PEP005.

Dr. Anderson, who is in private dermatology practice in Tyler, Texas, and his associates randomized 222 patients with 4- 8 visible AK lesions on the arm, shoulder, chest, back, or scalp, to one of four treatment groups. The primary end point was partial clearance, defined as the proportion of patients at day 57 with 75% reduction in the number of AK lesions identified at baseline.

Treatment with PEP005 gel once daily for 2 or 3 days produced significantly greater lesion clearance in a dose-dependent manner by all measures and at all dosing regimens, compared with a control vehicle applied once daily for 3 days.

The partial clearance rate was 22% for vehicle, 56% for ingenol mebutate gel 0.025% for 3 days, 62% for ingenol mebutate gel 0.05% for 2 days, and 75.4% for ingenol mebutate 0.05% for 3 days.

The proportion of patients at day 57 with complete clearance, defined as no clinically visible AK lesions, was 12%, 40%, 44%, and 54.4%, respectively.

All three active treatments were well tolerated, according to the investigators, one of whom was a Peplin employee. The most common lesion-site reactions on day 57 were erythema, experienced by 34% of 162 actively treated patients; flaking or scaling (29%); and crusting (9%).

Because AK lesions on the trunk and extremities historically are more difficult to treat than scalp lesions, the investigators performed an ad hoc analysis to compare outcomes in patients with scalp and nonscalp lesions, Dr. Michael Freeman of the Skin Centre, Gold Coast, Australia, and his associates said in a separate poster.

Overall, scalp treatment areas had a higher complete clearance rate than nonscalp treatment areas (57% vs. 42.4%), although the gel was better tolerated when applied to nonscalp areas, regardless of concentration or dosing schedule, the investigators wrote.

The maximum tolerated dose (MTD) for face or face and scalp AK was determined to be once-daily ingenol mebutate gel 0.025% for 2 days, according to a second study that evaluated six formulation strengths ranging from 0.0025% to 0.025% in 86 patients with lesions limited to the face or face and scalp.

At the MTD, 26 of 36 patients (72%) achieved partial clearance and 14 of the 36 (39%) achieved complete clearance.

Ingenol mebutate gel was well tolerated across all strengths, with erythema the most common lesion site reaction. Three patients experienced four serious adverse events, none considered treatment related, according to the investigators, one of whom was also a Peplin employee.

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SAN FRANCISCO — Intestinal-type adenocarcinoma of the ethmoid sinus appears to be strongly related to long-term occupational exposure to wood dust or leather dust, Dr. Stefano Riccio reported at the Seventh International Conference on Head and Neck Cancer.

In a case series involving 706 patients with malignant tumors of the paranasal sinuses, 92.2% of the patients with histologically confirmed adenocarcinoma of the ethmoid sinus acknowledged substantial exposure to one of these dusts, said Dr. Riccio of the National Cancer Institute of Milan.

Most patients had been exposed to organic dusts for 25–58 years in their jobs as woodworkers or shoemakers. But 17 patients reported only early and relatively limited exposure to organic dusts: from 4 to 18 years followed by 28–46 years before the appearance of disease.

In patients with nasal obstruction or small or occasional epistaxis, physicians should determine whether the patient had been exposed to any oncogenic agents in the past, Dr. Riccio recommended at the conference, which was sponsored by the American Head and Neck Society. If such exposure can be confirmed, adenocarcinoma of the ethmoid sinus should be part of the differential diagnosis.

Dr. Riccio pointed out that epidemiologists first noticed an association between wood dust and nasal cancer in 1965. But epidemiological studies rarely make anatomical distinctions among the paranasal sinuses.

On the other hand, physicians are aware that intestinal-type adenocarcinoma is peculiar to the ethmoid sinus. For the most part, however, they are unaware of the epidemiological connection with occupational exposure.

All patients in the case series were treated between 1987 and 2007 at the National Cancer Institute of Milan. The cancer originated in the ethmoid sinus 57% of the time and in the maxillary sinus 43% of the time.

Forty-five percent of the patients in the ethmoid group reported occupational exposure to wood or leather dust, compared with just 1.3% of the maxillary group, a significant difference.

Intestinal-type adenocarcinoma was the predominant histologic type in the ethmoid group, and was seen in 44% of those patients.

In comparison, squamous cell carcinoma was the most common histologic type in the maxillary group, and was seen in 35% of those patients.

In his review of the literature, Dr. Riccio found that the rate of adenocarcinoma among patients with malignant ethmoid tumors appears to be much higher in Europe than in North America. In five European case series, the rate ranged from 27% to 74%, with the lowest rate in the United Kingdom. In five North American case series, the rate ranged from 6% to 17%.

Dr. Riccio suggested the three possible explanations for this discrepancy. First, while the commonly accepted danger threshold for wood dust in Europe is 5 mg/m

Dr. Riccio stated that he had no conflicts of interest related to his presentation.

SAN FRANCISCO — Intestinal-type adenocarcinoma of the ethmoid sinus appears to be strongly related to long-term occupational exposure to wood dust or leather dust, Dr. Stefano Riccio reported at the Seventh International Conference on Head and Neck Cancer.

In a case series involving 706 patients with malignant tumors of the paranasal sinuses, 92.2% of the patients with histologically confirmed adenocarcinoma of the ethmoid sinus acknowledged substantial exposure to one of these dusts, said Dr. Riccio of the National Cancer Institute of Milan.

Most patients had been exposed to organic dusts for 25–58 years in their jobs as woodworkers or shoemakers. But 17 patients reported only early and relatively limited exposure to organic dusts: from 4 to 18 years followed by 28–46 years before the appearance of disease.

In patients with nasal obstruction or small or occasional epistaxis, physicians should determine whether the patient had been exposed to any oncogenic agents in the past, Dr. Riccio recommended at the conference, which was sponsored by the American Head and Neck Society. If such exposure can be confirmed, adenocarcinoma of the ethmoid sinus should be part of the differential diagnosis.

Dr. Riccio pointed out that epidemiologists first noticed an association between wood dust and nasal cancer in 1965. But epidemiological studies rarely make anatomical distinctions among the paranasal sinuses.

On the other hand, physicians are aware that intestinal-type adenocarcinoma is peculiar to the ethmoid sinus. For the most part, however, they are unaware of the epidemiological connection with occupational exposure.

All patients in the case series were treated between 1987 and 2007 at the National Cancer Institute of Milan. The cancer originated in the ethmoid sinus 57% of the time and in the maxillary sinus 43% of the time.

Forty-five percent of the patients in the ethmoid group reported occupational exposure to wood or leather dust, compared with just 1.3% of the maxillary group, a significant difference.

Intestinal-type adenocarcinoma was the predominant histologic type in the ethmoid group, and was seen in 44% of those patients.

In comparison, squamous cell carcinoma was the most common histologic type in the maxillary group, and was seen in 35% of those patients.

In his review of the literature, Dr. Riccio found that the rate of adenocarcinoma among patients with malignant ethmoid tumors appears to be much higher in Europe than in North America. In five European case series, the rate ranged from 27% to 74%, with the lowest rate in the United Kingdom. In five North American case series, the rate ranged from 6% to 17%.

Dr. Riccio suggested the three possible explanations for this discrepancy. First, while the commonly accepted danger threshold for wood dust in Europe is 5 mg/m

Dr. Riccio stated that he had no conflicts of interest related to his presentation.

SAN FRANCISCO — Intestinal-type adenocarcinoma of the ethmoid sinus appears to be strongly related to long-term occupational exposure to wood dust or leather dust, Dr. Stefano Riccio reported at the Seventh International Conference on Head and Neck Cancer.

In a case series involving 706 patients with malignant tumors of the paranasal sinuses, 92.2% of the patients with histologically confirmed adenocarcinoma of the ethmoid sinus acknowledged substantial exposure to one of these dusts, said Dr. Riccio of the National Cancer Institute of Milan.

Most patients had been exposed to organic dusts for 25–58 years in their jobs as woodworkers or shoemakers. But 17 patients reported only early and relatively limited exposure to organic dusts: from 4 to 18 years followed by 28–46 years before the appearance of disease.

In patients with nasal obstruction or small or occasional epistaxis, physicians should determine whether the patient had been exposed to any oncogenic agents in the past, Dr. Riccio recommended at the conference, which was sponsored by the American Head and Neck Society. If such exposure can be confirmed, adenocarcinoma of the ethmoid sinus should be part of the differential diagnosis.

Dr. Riccio pointed out that epidemiologists first noticed an association between wood dust and nasal cancer in 1965. But epidemiological studies rarely make anatomical distinctions among the paranasal sinuses.

On the other hand, physicians are aware that intestinal-type adenocarcinoma is peculiar to the ethmoid sinus. For the most part, however, they are unaware of the epidemiological connection with occupational exposure.

All patients in the case series were treated between 1987 and 2007 at the National Cancer Institute of Milan. The cancer originated in the ethmoid sinus 57% of the time and in the maxillary sinus 43% of the time.

Forty-five percent of the patients in the ethmoid group reported occupational exposure to wood or leather dust, compared with just 1.3% of the maxillary group, a significant difference.

Intestinal-type adenocarcinoma was the predominant histologic type in the ethmoid group, and was seen in 44% of those patients.

In comparison, squamous cell carcinoma was the most common histologic type in the maxillary group, and was seen in 35% of those patients.

In his review of the literature, Dr. Riccio found that the rate of adenocarcinoma among patients with malignant ethmoid tumors appears to be much higher in Europe than in North America. In five European case series, the rate ranged from 27% to 74%, with the lowest rate in the United Kingdom. In five North American case series, the rate ranged from 6% to 17%.

Dr. Riccio suggested the three possible explanations for this discrepancy. First, while the commonly accepted danger threshold for wood dust in Europe is 5 mg/m

Dr. Riccio stated that he had no conflicts of interest related to his presentation.

CHICAGO — A specific pattern of X and Y chromosome losses—and in particular the loss of an important tumor-suppression gene—was shown in a recent study to be associated with melanoma progression.

This "very new and very unexpected finding" could help explain gender differences that are seen in melanoma, such as the increased risk of death in men with melanoma, compared with women with melanoma, Dr. Alan Spatz said at the American Society of Clinical Oncology annual meeting, where he presented the findings.

Frozen sections from 48 melanomas—taken from 32 women and 16 men with a median follow-up of 4 years—were analyzed as part of a European Organisation for Research and Treatment of Cancer (EORTC) study. Analyses of DNA and mRNA were conducted; the end point was distant metastasis-free survival.

A significant correlation was found between DNA copy number and mRNA level for 1,455 genes (P less than .05). In the women's samples, losses in the X chromosome were significantly associated with distant metastasis-free survival (P = .009), and the affected X chromosome was always the inactive X.

In the men, losses in the Y chromosome were significantly associated with distant metastasis-free survival (P = .015), reported Dr. Spatz of Institut Gustave Roussy in Villejuif, France.

Further investigation to identify any particular gene or genes that fulfilled the criteria of being located on the X chromosome in women and escaping inactivation of X chromosome, as well as being located on the Y chromosome in men, showed that only the PPP2R3B gene, also know as PR48, did so.

The normalized expression of the gene, which is located on Xp22 in women and on Yp11 in men was found to be associated with distant metastasis-free survival at a "totally unexpected level of significance," (P = .0007), after adjusting for clinical and pathologic prognostic variables, including gender, age, ulceration, and thickness, Dr. Spatz said.

PR48 is a lesser-known subunit of a well-known and very important gene (serine/threonine protein phosphatase 2A) which he described as "kind of a gatekeeper in cell biology," he said.

PR48 mediates the dephosphorylation of CDC6 by phosphatase 2A and controls initiation of DNA replication in human cancer cells, especially melanoma, he explained.

The findings, along with those from other ongoing studies that are designed to help improve understanding of PPP2R3B biology, could potentially provide biologic clues regarding gender differences in melanoma progression and survival; the gender effect in melanoma is strong—men have been shown to have a relative excess risk of death of 1.87, compared with women with melanoma.

"We can conclude that there is a very specific pattern of X and Y chromosome losses associated with melanoma progression … and that PPP2R3B appears from this study to be a very important tumor suppression gene whose loss is associated with tumor progression.

"Does this explain the gender effect? Maybe if indeed we show that there is a differential frequency of inactivated X chromosome in females, as compared with Y chromosome—but this is still an open question," Dr. Spatz said.

In a discussion of the findings, Elizabeth Grimm, Ph.D., a professor at the University of Texas M.D. Anderson Cancer Center, Houston, called these and other emerging data a "snapshot of finest biomarker work in melanoma at this time." Dr. Spatz's work is particularly provocative, she said.

She asked, however, how—given the findings—one would explain that the incidence of melanoma in young women is higher than that in young men. The increased incidence in men only begins to become evident around age 50 years, she noted, questioning whether other lifestyle parameters are in play.

"Just food for thought," she said.

Dr. Grimm also noted that it would be interesting, should the findings be validated in the ongoing studies that Dr. Spatz mentioned, to see how they might change the course of treatment or provide prognostic information, and to determine whether some form of gene therapy to redeliver the X and Y chromosome losses could be developed.

CHICAGO — A specific pattern of X and Y chromosome losses—and in particular the loss of an important tumor-suppression gene—was shown in a recent study to be associated with melanoma progression.

This "very new and very unexpected finding" could help explain gender differences that are seen in melanoma, such as the increased risk of death in men with melanoma, compared with women with melanoma, Dr. Alan Spatz said at the American Society of Clinical Oncology annual meeting, where he presented the findings.

Frozen sections from 48 melanomas—taken from 32 women and 16 men with a median follow-up of 4 years—were analyzed as part of a European Organisation for Research and Treatment of Cancer (EORTC) study. Analyses of DNA and mRNA were conducted; the end point was distant metastasis-free survival.

A significant correlation was found between DNA copy number and mRNA level for 1,455 genes (P less than .05). In the women's samples, losses in the X chromosome were significantly associated with distant metastasis-free survival (P = .009), and the affected X chromosome was always the inactive X.

In the men, losses in the Y chromosome were significantly associated with distant metastasis-free survival (P = .015), reported Dr. Spatz of Institut Gustave Roussy in Villejuif, France.

Further investigation to identify any particular gene or genes that fulfilled the criteria of being located on the X chromosome in women and escaping inactivation of X chromosome, as well as being located on the Y chromosome in men, showed that only the PPP2R3B gene, also know as PR48, did so.

The normalized expression of the gene, which is located on Xp22 in women and on Yp11 in men was found to be associated with distant metastasis-free survival at a "totally unexpected level of significance," (P = .0007), after adjusting for clinical and pathologic prognostic variables, including gender, age, ulceration, and thickness, Dr. Spatz said.

PR48 is a lesser-known subunit of a well-known and very important gene (serine/threonine protein phosphatase 2A) which he described as "kind of a gatekeeper in cell biology," he said.

PR48 mediates the dephosphorylation of CDC6 by phosphatase 2A and controls initiation of DNA replication in human cancer cells, especially melanoma, he explained.

The findings, along with those from other ongoing studies that are designed to help improve understanding of PPP2R3B biology, could potentially provide biologic clues regarding gender differences in melanoma progression and survival; the gender effect in melanoma is strong—men have been shown to have a relative excess risk of death of 1.87, compared with women with melanoma.

"We can conclude that there is a very specific pattern of X and Y chromosome losses associated with melanoma progression … and that PPP2R3B appears from this study to be a very important tumor suppression gene whose loss is associated with tumor progression.

"Does this explain the gender effect? Maybe if indeed we show that there is a differential frequency of inactivated X chromosome in females, as compared with Y chromosome—but this is still an open question," Dr. Spatz said.

In a discussion of the findings, Elizabeth Grimm, Ph.D., a professor at the University of Texas M.D. Anderson Cancer Center, Houston, called these and other emerging data a "snapshot of finest biomarker work in melanoma at this time." Dr. Spatz's work is particularly provocative, she said.

She asked, however, how—given the findings—one would explain that the incidence of melanoma in young women is higher than that in young men. The increased incidence in men only begins to become evident around age 50 years, she noted, questioning whether other lifestyle parameters are in play.

"Just food for thought," she said.

Dr. Grimm also noted that it would be interesting, should the findings be validated in the ongoing studies that Dr. Spatz mentioned, to see how they might change the course of treatment or provide prognostic information, and to determine whether some form of gene therapy to redeliver the X and Y chromosome losses could be developed.

CHICAGO — A specific pattern of X and Y chromosome losses—and in particular the loss of an important tumor-suppression gene—was shown in a recent study to be associated with melanoma progression.

This "very new and very unexpected finding" could help explain gender differences that are seen in melanoma, such as the increased risk of death in men with melanoma, compared with women with melanoma, Dr. Alan Spatz said at the American Society of Clinical Oncology annual meeting, where he presented the findings.

Frozen sections from 48 melanomas—taken from 32 women and 16 men with a median follow-up of 4 years—were analyzed as part of a European Organisation for Research and Treatment of Cancer (EORTC) study. Analyses of DNA and mRNA were conducted; the end point was distant metastasis-free survival.

A significant correlation was found between DNA copy number and mRNA level for 1,455 genes (P less than .05). In the women's samples, losses in the X chromosome were significantly associated with distant metastasis-free survival (P = .009), and the affected X chromosome was always the inactive X.

In the men, losses in the Y chromosome were significantly associated with distant metastasis-free survival (P = .015), reported Dr. Spatz of Institut Gustave Roussy in Villejuif, France.

Further investigation to identify any particular gene or genes that fulfilled the criteria of being located on the X chromosome in women and escaping inactivation of X chromosome, as well as being located on the Y chromosome in men, showed that only the PPP2R3B gene, also know as PR48, did so.

The normalized expression of the gene, which is located on Xp22 in women and on Yp11 in men was found to be associated with distant metastasis-free survival at a "totally unexpected level of significance," (P = .0007), after adjusting for clinical and pathologic prognostic variables, including gender, age, ulceration, and thickness, Dr. Spatz said.

PR48 is a lesser-known subunit of a well-known and very important gene (serine/threonine protein phosphatase 2A) which he described as "kind of a gatekeeper in cell biology," he said.

PR48 mediates the dephosphorylation of CDC6 by phosphatase 2A and controls initiation of DNA replication in human cancer cells, especially melanoma, he explained.

The findings, along with those from other ongoing studies that are designed to help improve understanding of PPP2R3B biology, could potentially provide biologic clues regarding gender differences in melanoma progression and survival; the gender effect in melanoma is strong—men have been shown to have a relative excess risk of death of 1.87, compared with women with melanoma.

"We can conclude that there is a very specific pattern of X and Y chromosome losses associated with melanoma progression … and that PPP2R3B appears from this study to be a very important tumor suppression gene whose loss is associated with tumor progression.

"Does this explain the gender effect? Maybe if indeed we show that there is a differential frequency of inactivated X chromosome in females, as compared with Y chromosome—but this is still an open question," Dr. Spatz said.

In a discussion of the findings, Elizabeth Grimm, Ph.D., a professor at the University of Texas M.D. Anderson Cancer Center, Houston, called these and other emerging data a "snapshot of finest biomarker work in melanoma at this time." Dr. Spatz's work is particularly provocative, she said.

She asked, however, how—given the findings—one would explain that the incidence of melanoma in young women is higher than that in young men. The increased incidence in men only begins to become evident around age 50 years, she noted, questioning whether other lifestyle parameters are in play.

"Just food for thought," she said.

Dr. Grimm also noted that it would be interesting, should the findings be validated in the ongoing studies that Dr. Spatz mentioned, to see how they might change the course of treatment or provide prognostic information, and to determine whether some form of gene therapy to redeliver the X and Y chromosome losses could be developed.

CHICAGO — Micro-RNA-21 and micro-RNA-155 are expressed at significantly higher levels in primary malignant melanoma tumor samples than in samples from benign nevi—and in indeterminate melanocytic lesions with an aggressive histological phenotype, according to data presented at the American Society of Clinical Oncology annual meeting.

Samples from eight dermal nevi, 28 malignant melanomas, and 49 pathologically indeterminate melanocytic lesions were evaluated using real-time polymerase chain reaction. Investigators found a mean 7.6-fold increase in micro-RNA-21 expression (P = .0001) and a mean 13.3-fold increase (P = .0001) in micro-RNA-155 expression, compared with the benign nevus samples, reported Gregory B. Lesinski, Ph.D., of Ohio State University, Columbus.

Another potential biomarker—micro-RNA-21b—showed a trend toward increased expression, but the difference did not reach statistical significance in this small sample size (P = .07). However, micro-RNA-21b remains of interest, Dr. Lesinski noted.

Micro-RNA-21 and micro-RNA-155 also appear to be expressed at higher levels in certain indeterminate melanocytic lesions. Indeterminate lesions, including deep penetrating nevi, dysplastic nevi, and Spitz nevi, pose a particular challenge in that diagnosis and determination of the appropriate course of action are uncertain.

A false-positive diagnosis could lead to unnecessary treatment; a false-negative diagnosis could lead to undertreatment and increased risk of melanoma development.

In this study, expression of micro-RNA-21 and micro-RNA-155 was analyzed in indeterminate lesions with more than one mitosis per 10x high-power field.

When they were compared with those with less than one mitosis per 10x high-power field, there was significantly higher expression of micro-RNA-21 (P = .0005) and micro-RNA-155 (P = .04).

Melanocytic lesions that were greater than 1 mm in depth, compared with thinner lesions, also had significantly higher levels of micro-RNA-155 (P = .01), suggesting these might have more malignant potential; micro-RNA-21 was higher in the thicker lesions as well, but the difference did not reach statistical significance, Dr. Lesinski said.

In a subset of 13 patients with indeterminate lesions whose lesions were considered suspicious enough that the patients were sent for sentinel node biopsy, micro-RNA-21 and micro-RNA-155 expression were compared with expression in benign nevi—in both those that proved node positive and those that proved node negative.

Micro-RNA expression was significantly higher in the lesions from node-positive patients, compared with expression in benign nevi (mean 6.5-fold increase), than in node-negative patients, compared with expression in benign nevi (1.3-fold increase).

"Surprisingly, we didn't find the same relationship for micro-RNA-155; the data were highly variable [for micro-RNA-155] regardless of whether the patients were node negative or node positive," said Dr. Lesinski, who reported he has no disclosures relevant to the data he presented.

These data are "very preliminary," he added, noting that the sample size for this portion of the study is being expanded to include at least 50 patients to make a more accurate statistical determination about the expression of these micro-RNAs.

"Nonetheless, these data are very enticing to us, and they suggest that micro-RNA-21, at least, may in fact be a relevant marker that can be used to complement the traditional histological analyses used to diagnose these lesions," he said.

The expression of micro-RNAs—a group of more than 200 recently identified noncoding molecules considered to be a new class of oncogenes—is altered in many types of tumors.

This study is among the first to explore this expression in melanoma. Studies to further assess the potential value of micro-RNAs as diagnostic and prognostic tools in melanoma are ongoing, Dr. Lesinski said.

During a discussion of Dr. Lesinski's findings and those from other melanoma biomarker studies, Elizabeth Grimm, Ph.D., said they are part of a "fabulous set of new data."

Dr. Lesinski's findings regarding indeterminate lesions are particularly important given the therapeutic dilemma they pose, she said.

She expressed concern, however, about difficulty in determining whether micro-RNA expression is increased in melanomas, compared with indeterminate lesions. Differences were marked between melanoma and benign nevi, but based on her review of the data, it appears there was little difference in expression between melanoma and indeterminate lesions, Dr. Grimm said, adding that research regarding other micro-RNAs should continue.

She also noted that she is curious about whether there is a micro-RNA signature that adds value to the current staging system and markers commonly used, and whether micro-RNAs can be used independently of common diagnostic markers used by pathologists, such as MAGE, MART, and S100B.

While many questions remain, she applauded the research effort, noting that there are valid markers in other tumor types; thus, the "noble" efforts to identify molecular markers for melanoma are worthwhile. "We're not just dreaming—we will have them for melanoma some day," said Dr. Grimm of M.D. Anderson Cancer Center, Houston.

CHICAGO — Micro-RNA-21 and micro-RNA-155 are expressed at significantly higher levels in primary malignant melanoma tumor samples than in samples from benign nevi—and in indeterminate melanocytic lesions with an aggressive histological phenotype, according to data presented at the American Society of Clinical Oncology annual meeting.

Samples from eight dermal nevi, 28 malignant melanomas, and 49 pathologically indeterminate melanocytic lesions were evaluated using real-time polymerase chain reaction. Investigators found a mean 7.6-fold increase in micro-RNA-21 expression (P = .0001) and a mean 13.3-fold increase (P = .0001) in micro-RNA-155 expression, compared with the benign nevus samples, reported Gregory B. Lesinski, Ph.D., of Ohio State University, Columbus.

Another potential biomarker—micro-RNA-21b—showed a trend toward increased expression, but the difference did not reach statistical significance in this small sample size (P = .07). However, micro-RNA-21b remains of interest, Dr. Lesinski noted.

Micro-RNA-21 and micro-RNA-155 also appear to be expressed at higher levels in certain indeterminate melanocytic lesions. Indeterminate lesions, including deep penetrating nevi, dysplastic nevi, and Spitz nevi, pose a particular challenge in that diagnosis and determination of the appropriate course of action are uncertain.

A false-positive diagnosis could lead to unnecessary treatment; a false-negative diagnosis could lead to undertreatment and increased risk of melanoma development.

In this study, expression of micro-RNA-21 and micro-RNA-155 was analyzed in indeterminate lesions with more than one mitosis per 10x high-power field.

When they were compared with those with less than one mitosis per 10x high-power field, there was significantly higher expression of micro-RNA-21 (P = .0005) and micro-RNA-155 (P = .04).

Melanocytic lesions that were greater than 1 mm in depth, compared with thinner lesions, also had significantly higher levels of micro-RNA-155 (P = .01), suggesting these might have more malignant potential; micro-RNA-21 was higher in the thicker lesions as well, but the difference did not reach statistical significance, Dr. Lesinski said.

In a subset of 13 patients with indeterminate lesions whose lesions were considered suspicious enough that the patients were sent for sentinel node biopsy, micro-RNA-21 and micro-RNA-155 expression were compared with expression in benign nevi—in both those that proved node positive and those that proved node negative.

Micro-RNA expression was significantly higher in the lesions from node-positive patients, compared with expression in benign nevi (mean 6.5-fold increase), than in node-negative patients, compared with expression in benign nevi (1.3-fold increase).

"Surprisingly, we didn't find the same relationship for micro-RNA-155; the data were highly variable [for micro-RNA-155] regardless of whether the patients were node negative or node positive," said Dr. Lesinski, who reported he has no disclosures relevant to the data he presented.

These data are "very preliminary," he added, noting that the sample size for this portion of the study is being expanded to include at least 50 patients to make a more accurate statistical determination about the expression of these micro-RNAs.

"Nonetheless, these data are very enticing to us, and they suggest that micro-RNA-21, at least, may in fact be a relevant marker that can be used to complement the traditional histological analyses used to diagnose these lesions," he said.

The expression of micro-RNAs—a group of more than 200 recently identified noncoding molecules considered to be a new class of oncogenes—is altered in many types of tumors.

This study is among the first to explore this expression in melanoma. Studies to further assess the potential value of micro-RNAs as diagnostic and prognostic tools in melanoma are ongoing, Dr. Lesinski said.

During a discussion of Dr. Lesinski's findings and those from other melanoma biomarker studies, Elizabeth Grimm, Ph.D., said they are part of a "fabulous set of new data."

Dr. Lesinski's findings regarding indeterminate lesions are particularly important given the therapeutic dilemma they pose, she said.

She expressed concern, however, about difficulty in determining whether micro-RNA expression is increased in melanomas, compared with indeterminate lesions. Differences were marked between melanoma and benign nevi, but based on her review of the data, it appears there was little difference in expression between melanoma and indeterminate lesions, Dr. Grimm said, adding that research regarding other micro-RNAs should continue.

She also noted that she is curious about whether there is a micro-RNA signature that adds value to the current staging system and markers commonly used, and whether micro-RNAs can be used independently of common diagnostic markers used by pathologists, such as MAGE, MART, and S100B.

While many questions remain, she applauded the research effort, noting that there are valid markers in other tumor types; thus, the "noble" efforts to identify molecular markers for melanoma are worthwhile. "We're not just dreaming—we will have them for melanoma some day," said Dr. Grimm of M.D. Anderson Cancer Center, Houston.

CHICAGO — Micro-RNA-21 and micro-RNA-155 are expressed at significantly higher levels in primary malignant melanoma tumor samples than in samples from benign nevi—and in indeterminate melanocytic lesions with an aggressive histological phenotype, according to data presented at the American Society of Clinical Oncology annual meeting.

Samples from eight dermal nevi, 28 malignant melanomas, and 49 pathologically indeterminate melanocytic lesions were evaluated using real-time polymerase chain reaction. Investigators found a mean 7.6-fold increase in micro-RNA-21 expression (P = .0001) and a mean 13.3-fold increase (P = .0001) in micro-RNA-155 expression, compared with the benign nevus samples, reported Gregory B. Lesinski, Ph.D., of Ohio State University, Columbus.

Another potential biomarker—micro-RNA-21b—showed a trend toward increased expression, but the difference did not reach statistical significance in this small sample size (P = .07). However, micro-RNA-21b remains of interest, Dr. Lesinski noted.

Micro-RNA-21 and micro-RNA-155 also appear to be expressed at higher levels in certain indeterminate melanocytic lesions. Indeterminate lesions, including deep penetrating nevi, dysplastic nevi, and Spitz nevi, pose a particular challenge in that diagnosis and determination of the appropriate course of action are uncertain.

A false-positive diagnosis could lead to unnecessary treatment; a false-negative diagnosis could lead to undertreatment and increased risk of melanoma development.

In this study, expression of micro-RNA-21 and micro-RNA-155 was analyzed in indeterminate lesions with more than one mitosis per 10x high-power field.

When they were compared with those with less than one mitosis per 10x high-power field, there was significantly higher expression of micro-RNA-21 (P = .0005) and micro-RNA-155 (P = .04).

Melanocytic lesions that were greater than 1 mm in depth, compared with thinner lesions, also had significantly higher levels of micro-RNA-155 (P = .01), suggesting these might have more malignant potential; micro-RNA-21 was higher in the thicker lesions as well, but the difference did not reach statistical significance, Dr. Lesinski said.

In a subset of 13 patients with indeterminate lesions whose lesions were considered suspicious enough that the patients were sent for sentinel node biopsy, micro-RNA-21 and micro-RNA-155 expression were compared with expression in benign nevi—in both those that proved node positive and those that proved node negative.

Micro-RNA expression was significantly higher in the lesions from node-positive patients, compared with expression in benign nevi (mean 6.5-fold increase), than in node-negative patients, compared with expression in benign nevi (1.3-fold increase).

"Surprisingly, we didn't find the same relationship for micro-RNA-155; the data were highly variable [for micro-RNA-155] regardless of whether the patients were node negative or node positive," said Dr. Lesinski, who reported he has no disclosures relevant to the data he presented.

These data are "very preliminary," he added, noting that the sample size for this portion of the study is being expanded to include at least 50 patients to make a more accurate statistical determination about the expression of these micro-RNAs.

"Nonetheless, these data are very enticing to us, and they suggest that micro-RNA-21, at least, may in fact be a relevant marker that can be used to complement the traditional histological analyses used to diagnose these lesions," he said.

The expression of micro-RNAs—a group of more than 200 recently identified noncoding molecules considered to be a new class of oncogenes—is altered in many types of tumors.

This study is among the first to explore this expression in melanoma. Studies to further assess the potential value of micro-RNAs as diagnostic and prognostic tools in melanoma are ongoing, Dr. Lesinski said.

During a discussion of Dr. Lesinski's findings and those from other melanoma biomarker studies, Elizabeth Grimm, Ph.D., said they are part of a "fabulous set of new data."

Dr. Lesinski's findings regarding indeterminate lesions are particularly important given the therapeutic dilemma they pose, she said.

She expressed concern, however, about difficulty in determining whether micro-RNA expression is increased in melanomas, compared with indeterminate lesions. Differences were marked between melanoma and benign nevi, but based on her review of the data, it appears there was little difference in expression between melanoma and indeterminate lesions, Dr. Grimm said, adding that research regarding other micro-RNAs should continue.

She also noted that she is curious about whether there is a micro-RNA signature that adds value to the current staging system and markers commonly used, and whether micro-RNAs can be used independently of common diagnostic markers used by pathologists, such as MAGE, MART, and S100B.

While many questions remain, she applauded the research effort, noting that there are valid markers in other tumor types; thus, the "noble" efforts to identify molecular markers for melanoma are worthwhile. "We're not just dreaming—we will have them for melanoma some day," said Dr. Grimm of M.D. Anderson Cancer Center, Houston.

SAN FRANCISCO — Patients who received adjuvant radiotherapy following surgery for metastatic cutaneous squamous cell carcinoma survived more than twice as long as did those who did not receive radiotherapy in a small retrospective study.

The difference between median survival of 23 months with adjuvant radiotherapy and 10 months without the extra treatment was statistically significant, Dr. Babak Givi reported at the Seventh International Conference on Head and Neck Cancer.

Patients receiving adjuvant radiotherapy were more than 80% less likely to die than were those who did not receive this adjuvant treatment, said Dr. Givi of Oregon Health and Science University, Portland.

Surgery followed by radiotherapy has long been a standard treatment for metastatic squamous cell carcinoma of the head and neck, but Dr. Givi noted that there is a paucity of experimental data on its efficacy. Given the fact that this regimen is aggressive and carries a high degree of morbidity, he and his colleagues conducted a retrospective study involving 51 patients who received surgical treatment for metastatic squamous cell carcinoma between 1993 and 2008. Thirty of the patients received adjuvant radiotherapy.

The patients' median age was 73 years, and 47 patients were male. The disease was recurrent in 8 patients and previously untreated in 43. Those whose disease had recurred survived for a median of 14 months compared with 31 months among those who had not previously been treated.

After adjusting for age, immunosuppression, tumor characteristics, and recurrent disease in a multivariate analysis, the investigators found that patients with recurrent disease were almost three times as likely to die as were those without.

The conference was sponsored by the American Head and Neck Society.

SAN FRANCISCO — Patients who received adjuvant radiotherapy following surgery for metastatic cutaneous squamous cell carcinoma survived more than twice as long as did those who did not receive radiotherapy in a small retrospective study.

The difference between median survival of 23 months with adjuvant radiotherapy and 10 months without the extra treatment was statistically significant, Dr. Babak Givi reported at the Seventh International Conference on Head and Neck Cancer.

Patients receiving adjuvant radiotherapy were more than 80% less likely to die than were those who did not receive this adjuvant treatment, said Dr. Givi of Oregon Health and Science University, Portland.

Surgery followed by radiotherapy has long been a standard treatment for metastatic squamous cell carcinoma of the head and neck, but Dr. Givi noted that there is a paucity of experimental data on its efficacy. Given the fact that this regimen is aggressive and carries a high degree of morbidity, he and his colleagues conducted a retrospective study involving 51 patients who received surgical treatment for metastatic squamous cell carcinoma between 1993 and 2008. Thirty of the patients received adjuvant radiotherapy.

The patients' median age was 73 years, and 47 patients were male. The disease was recurrent in 8 patients and previously untreated in 43. Those whose disease had recurred survived for a median of 14 months compared with 31 months among those who had not previously been treated.

After adjusting for age, immunosuppression, tumor characteristics, and recurrent disease in a multivariate analysis, the investigators found that patients with recurrent disease were almost three times as likely to die as were those without.

The conference was sponsored by the American Head and Neck Society.

SAN FRANCISCO — Patients who received adjuvant radiotherapy following surgery for metastatic cutaneous squamous cell carcinoma survived more than twice as long as did those who did not receive radiotherapy in a small retrospective study.

The difference between median survival of 23 months with adjuvant radiotherapy and 10 months without the extra treatment was statistically significant, Dr. Babak Givi reported at the Seventh International Conference on Head and Neck Cancer.

Patients receiving adjuvant radiotherapy were more than 80% less likely to die than were those who did not receive this adjuvant treatment, said Dr. Givi of Oregon Health and Science University, Portland.

Surgery followed by radiotherapy has long been a standard treatment for metastatic squamous cell carcinoma of the head and neck, but Dr. Givi noted that there is a paucity of experimental data on its efficacy. Given the fact that this regimen is aggressive and carries a high degree of morbidity, he and his colleagues conducted a retrospective study involving 51 patients who received surgical treatment for metastatic squamous cell carcinoma between 1993 and 2008. Thirty of the patients received adjuvant radiotherapy.

The patients' median age was 73 years, and 47 patients were male. The disease was recurrent in 8 patients and previously untreated in 43. Those whose disease had recurred survived for a median of 14 months compared with 31 months among those who had not previously been treated.

After adjusting for age, immunosuppression, tumor characteristics, and recurrent disease in a multivariate analysis, the investigators found that patients with recurrent disease were almost three times as likely to die as were those without.

The conference was sponsored by the American Head and Neck Society.

SAN FRANCISCO — A 5-year local control rate is possible with or without skin excision in squamous cell carcinoma of the buccal mucosa, according to a retrospective study of 331 patients.

When patients are properly selected for skin preservation or sacrifice on the basis of surgical margins more or less than 1 cm, there are no statistically significant differences in survival, Dr. Chun-Ta Liao and colleagues reported. In patients treated with surgery alone, the 5-year survival rate was 94% with skin excision and 91% without skin excision. In patients treated with surgery plus adjuvant radiotherapy or chemotherapy, the 5-year survival rate was 82% with skin excision and 85% without skin excision.

While it's generally accepted that bone excisions are often indicated in this form of cancer, controversy remains, said Dr. Liao. Skin excision significantly affects the patient's appearance and may contribute to oral incompetence, so physicians prefer to preserve the cheek skin if doing so would not increase mortality.

The study, by Dr. Liao of Chang Gung University, Taoyuan, Taiwan, and colleagues, was presented at the Seventh International Conference on Head and Neck Cancer.

The investigators examined records from 331 patients with squamous cell carcinoma of the buccal mucosa. Of those, 149 received surgery alone and 182 received surgery followed by adjuvant radiotherapy or radiotherapy plus chemotherapy.

Patients received skin-preserving procedures when the distance between the tumor and the skin was 13 mm or greater. This was possible for 69.5% of the patients, Dr. Liao reported at the meeting sponsored by the American Head and Neck Society.

In another part of the study, the investigators determined that a surgical margin of 4 mm or below was an independent predictor of adverse outcome, leading to an 81% increase in the risk of local recurrence in patients receiving surgery alone and a 33% increase in risk in patients receiving surgery plus adjuvant therapy.

Dr. Liao said the investigators had no conflicts of interest regarding the study.

SAN FRANCISCO — A 5-year local control rate is possible with or without skin excision in squamous cell carcinoma of the buccal mucosa, according to a retrospective study of 331 patients.

When patients are properly selected for skin preservation or sacrifice on the basis of surgical margins more or less than 1 cm, there are no statistically significant differences in survival, Dr. Chun-Ta Liao and colleagues reported. In patients treated with surgery alone, the 5-year survival rate was 94% with skin excision and 91% without skin excision. In patients treated with surgery plus adjuvant radiotherapy or chemotherapy, the 5-year survival rate was 82% with skin excision and 85% without skin excision.

While it's generally accepted that bone excisions are often indicated in this form of cancer, controversy remains, said Dr. Liao. Skin excision significantly affects the patient's appearance and may contribute to oral incompetence, so physicians prefer to preserve the cheek skin if doing so would not increase mortality.

The study, by Dr. Liao of Chang Gung University, Taoyuan, Taiwan, and colleagues, was presented at the Seventh International Conference on Head and Neck Cancer.

The investigators examined records from 331 patients with squamous cell carcinoma of the buccal mucosa. Of those, 149 received surgery alone and 182 received surgery followed by adjuvant radiotherapy or radiotherapy plus chemotherapy.

Patients received skin-preserving procedures when the distance between the tumor and the skin was 13 mm or greater. This was possible for 69.5% of the patients, Dr. Liao reported at the meeting sponsored by the American Head and Neck Society.

In another part of the study, the investigators determined that a surgical margin of 4 mm or below was an independent predictor of adverse outcome, leading to an 81% increase in the risk of local recurrence in patients receiving surgery alone and a 33% increase in risk in patients receiving surgery plus adjuvant therapy.

Dr. Liao said the investigators had no conflicts of interest regarding the study.

SAN FRANCISCO — A 5-year local control rate is possible with or without skin excision in squamous cell carcinoma of the buccal mucosa, according to a retrospective study of 331 patients.

When patients are properly selected for skin preservation or sacrifice on the basis of surgical margins more or less than 1 cm, there are no statistically significant differences in survival, Dr. Chun-Ta Liao and colleagues reported. In patients treated with surgery alone, the 5-year survival rate was 94% with skin excision and 91% without skin excision. In patients treated with surgery plus adjuvant radiotherapy or chemotherapy, the 5-year survival rate was 82% with skin excision and 85% without skin excision.

While it's generally accepted that bone excisions are often indicated in this form of cancer, controversy remains, said Dr. Liao. Skin excision significantly affects the patient's appearance and may contribute to oral incompetence, so physicians prefer to preserve the cheek skin if doing so would not increase mortality.

The study, by Dr. Liao of Chang Gung University, Taoyuan, Taiwan, and colleagues, was presented at the Seventh International Conference on Head and Neck Cancer.

The investigators examined records from 331 patients with squamous cell carcinoma of the buccal mucosa. Of those, 149 received surgery alone and 182 received surgery followed by adjuvant radiotherapy or radiotherapy plus chemotherapy.

Patients received skin-preserving procedures when the distance between the tumor and the skin was 13 mm or greater. This was possible for 69.5% of the patients, Dr. Liao reported at the meeting sponsored by the American Head and Neck Society.

In another part of the study, the investigators determined that a surgical margin of 4 mm or below was an independent predictor of adverse outcome, leading to an 81% increase in the risk of local recurrence in patients receiving surgery alone and a 33% increase in risk in patients receiving surgery plus adjuvant therapy.

Dr. Liao said the investigators had no conflicts of interest regarding the study.

The Dermatology Foundation has conferred its Lifetime Career Educator Award on Dr. Irwin M. Braverman, professor of dermatology at Yale University School of Medicine. According to the foundation, "The award celebrates Dr. Braverman's distinguished career and the high standard he has set for the next generation of teachers in all areas of dermatology." For more information, visit www.dermatologyfoundation.org

The Dermatology Foundation has conferred its Lifetime Career Educator Award on Dr. Irwin M. Braverman, professor of dermatology at Yale University School of Medicine. According to the foundation, "The award celebrates Dr. Braverman's distinguished career and the high standard he has set for the next generation of teachers in all areas of dermatology." For more information, visit www.dermatologyfoundation.org

The Dermatology Foundation has conferred its Lifetime Career Educator Award on Dr. Irwin M. Braverman, professor of dermatology at Yale University School of Medicine. According to the foundation, "The award celebrates Dr. Braverman's distinguished career and the high standard he has set for the next generation of teachers in all areas of dermatology." For more information, visit www.dermatologyfoundation.org

SAN FRANCISCO — While the relationship of the human papillomavirus to cervical cancer is well known among the public and in the medical profession, it is less commonly recognized that oral HPV appears to be associated with head and neck cancers. Even among the cognoscenti, there is a good deal of confusion about the details of this association.

At the Seventh International Conference on Head and Neck Cancer, Dr. Maura L. Gillison of Johns Hopkins University, Baltimore, reviewed current studies to answer some of the most frequently asked questions about HPV and cancers of the head and neck:

▸ Which HPV types are most associated with cancers of the head and neck? HPV-16 is the most common cause of cervical cancer, accounting for about 54% of these cancers, followed by HPV-18 and HPV-45. HPV-16 may be even more prominent among cancers of the head and neck, with a 92% association in one study.

▸ What risk of cancer is associated with oral HPV infection? Published studies show little agreement on the magnitude of the risk associated with oral HPV-16, although all the studies that Dr. Gillison reviewed found statistically significant increases. The odds ratios in published studies range from 1.7 for all the head and neck cancers to 32.3 for cancers of the oropharynx to 99.3 for cancers of the tonsil. Dr. Gillison estimated the overall increase in the risk of oropharyngeal cancer from HPV-16 infection to be about 15-fold over the risk in people who are not infected.

▸ How common is oral HPV infection? Estimates of the prevalence of HPV infection in control populations range from 3% to 18%.

▸ What are the risk factors for oral HPV infection? As in urogenital infection, sexual behavior appears to be the prime culprit in oral HPV infection, although peripartum transmission has been documented. Several studies have found HPV-16-positive head and neck cancers to be associated with a history of sexually transmitted disease, a history of casual sex, infrequent condom use, infrequent barrier use during oral sex, the number of sexual partners, and the number of oral sex partners.

▸ How does oral infection relate to cervical infection? Oral HPV infection is about three times as likely in women with cervical infections, but in the overwhelming majority of these women—94% according to one study—different types of HPV are responsible for their oral and urogenital infections.

▸ How long is a patient with HPV-positive cancer infectious? Studies have found oral HPV infections to persist for about 2 years following treatment for head and neck cancers. These infections have not been associated with recurrences or second primary cancers, however.

▸ Will the HPV vaccine have any effect on oral HPV infection? There is no direct evidence bearing on this question, but the indirect evidence is encouraging. Following vaccination, HPV-16 IgG can be detected in oral fluid, and oral HPV-16 is seropositive with cervical HPV-16.

Dr. Gillison serves as a consultant to, receives research funding from, and collaborates with scientists employed by Merck & Co. The conference was sponsored by the American Head and Neck Society.

SAN FRANCISCO — While the relationship of the human papillomavirus to cervical cancer is well known among the public and in the medical profession, it is less commonly recognized that oral HPV appears to be associated with head and neck cancers. Even among the cognoscenti, there is a good deal of confusion about the details of this association.

At the Seventh International Conference on Head and Neck Cancer, Dr. Maura L. Gillison of Johns Hopkins University, Baltimore, reviewed current studies to answer some of the most frequently asked questions about HPV and cancers of the head and neck:

▸ Which HPV types are most associated with cancers of the head and neck? HPV-16 is the most common cause of cervical cancer, accounting for about 54% of these cancers, followed by HPV-18 and HPV-45. HPV-16 may be even more prominent among cancers of the head and neck, with a 92% association in one study.

▸ What risk of cancer is associated with oral HPV infection? Published studies show little agreement on the magnitude of the risk associated with oral HPV-16, although all the studies that Dr. Gillison reviewed found statistically significant increases. The odds ratios in published studies range from 1.7 for all the head and neck cancers to 32.3 for cancers of the oropharynx to 99.3 for cancers of the tonsil. Dr. Gillison estimated the overall increase in the risk of oropharyngeal cancer from HPV-16 infection to be about 15-fold over the risk in people who are not infected.

▸ How common is oral HPV infection? Estimates of the prevalence of HPV infection in control populations range from 3% to 18%.

▸ What are the risk factors for oral HPV infection? As in urogenital infection, sexual behavior appears to be the prime culprit in oral HPV infection, although peripartum transmission has been documented. Several studies have found HPV-16-positive head and neck cancers to be associated with a history of sexually transmitted disease, a history of casual sex, infrequent condom use, infrequent barrier use during oral sex, the number of sexual partners, and the number of oral sex partners.

▸ How does oral infection relate to cervical infection? Oral HPV infection is about three times as likely in women with cervical infections, but in the overwhelming majority of these women—94% according to one study—different types of HPV are responsible for their oral and urogenital infections.

▸ How long is a patient with HPV-positive cancer infectious? Studies have found oral HPV infections to persist for about 2 years following treatment for head and neck cancers. These infections have not been associated with recurrences or second primary cancers, however.

▸ Will the HPV vaccine have any effect on oral HPV infection? There is no direct evidence bearing on this question, but the indirect evidence is encouraging. Following vaccination, HPV-16 IgG can be detected in oral fluid, and oral HPV-16 is seropositive with cervical HPV-16.

Dr. Gillison serves as a consultant to, receives research funding from, and collaborates with scientists employed by Merck & Co. The conference was sponsored by the American Head and Neck Society.

SAN FRANCISCO — While the relationship of the human papillomavirus to cervical cancer is well known among the public and in the medical profession, it is less commonly recognized that oral HPV appears to be associated with head and neck cancers. Even among the cognoscenti, there is a good deal of confusion about the details of this association.

At the Seventh International Conference on Head and Neck Cancer, Dr. Maura L. Gillison of Johns Hopkins University, Baltimore, reviewed current studies to answer some of the most frequently asked questions about HPV and cancers of the head and neck:

▸ Which HPV types are most associated with cancers of the head and neck? HPV-16 is the most common cause of cervical cancer, accounting for about 54% of these cancers, followed by HPV-18 and HPV-45. HPV-16 may be even more prominent among cancers of the head and neck, with a 92% association in one study.

▸ What risk of cancer is associated with oral HPV infection? Published studies show little agreement on the magnitude of the risk associated with oral HPV-16, although all the studies that Dr. Gillison reviewed found statistically significant increases. The odds ratios in published studies range from 1.7 for all the head and neck cancers to 32.3 for cancers of the oropharynx to 99.3 for cancers of the tonsil. Dr. Gillison estimated the overall increase in the risk of oropharyngeal cancer from HPV-16 infection to be about 15-fold over the risk in people who are not infected.

▸ How common is oral HPV infection? Estimates of the prevalence of HPV infection in control populations range from 3% to 18%.

▸ What are the risk factors for oral HPV infection? As in urogenital infection, sexual behavior appears to be the prime culprit in oral HPV infection, although peripartum transmission has been documented. Several studies have found HPV-16-positive head and neck cancers to be associated with a history of sexually transmitted disease, a history of casual sex, infrequent condom use, infrequent barrier use during oral sex, the number of sexual partners, and the number of oral sex partners.

▸ How does oral infection relate to cervical infection? Oral HPV infection is about three times as likely in women with cervical infections, but in the overwhelming majority of these women—94% according to one study—different types of HPV are responsible for their oral and urogenital infections.

▸ How long is a patient with HPV-positive cancer infectious? Studies have found oral HPV infections to persist for about 2 years following treatment for head and neck cancers. These infections have not been associated with recurrences or second primary cancers, however.

▸ Will the HPV vaccine have any effect on oral HPV infection? There is no direct evidence bearing on this question, but the indirect evidence is encouraging. Following vaccination, HPV-16 IgG can be detected in oral fluid, and oral HPV-16 is seropositive with cervical HPV-16.

Dr. Gillison serves as a consultant to, receives research funding from, and collaborates with scientists employed by Merck & Co. The conference was sponsored by the American Head and Neck Society.

MONTREAL — Formation of an international confocal microscopy group, software that aids the detection and mapping of skin lesions, and introduction of a handheld device are among recent advances to aid in the diagnosis of lentigo maligna and other lesions in real time.

Researchers hope widespread adoption of confocal laser microscopy progress will permit further early diagnoses of cutaneous melanoma and other lesions at the bedside. "It is critical to do biopsies early. If you believe cancer starts from a single cell, you can diagnose it early [with confocal laser microscopy]. That is what we are working on now," Dr. Richard Langley said.

Described as a "living skin biopsy" by some, microscopy is not new. Pathologists have employed the intensely focused light to examine tissue specimens since the 1950s, he said. There is a limitation in live patients, however. "We cannot go through a patient's skin, so we deal with reflective light. We still have confocal concepts, but we have real-time results," Dr. Langley said at the annual conference of the Canadian Dermatology Association.

Dr. Langley and his colleagues were the first to report use of confocal laser microscopy in a series of 40 dermatology patients with superficial melanoma (J. Am. Acad. Dermatol. 2001;45:365–76).

Others have since validated that microscopy distinguishes between malignant and benign lesions in vivo. To date, studies include more than 400 patients, said Dr. Langley of Dalhousie University, Halifax, N.S.

Last year, he and his associates published the first prospective study to compare microscopy with dermoscopy. "We decided to see if we can do a prospective, blinded, single-institution study," he said.

They assessed 125 patients with suspicious pigmented lesions using both technologies, followed by a confirmatory biopsy (Dermatology 2007;215:365–72). They detected a total of 88 melanotic nevi and 37 melanomas. "Sensitivity was higher with confocal versus dermoscopy [97% vs. 89%, respectively]. The specificity was about the same [83% vs. 84%]," Dr. Langley said. "We missed one melanoma with the confocal technology, so it was not perfect."

For dermatologists accustomed to reading cross-sectional biopsies, it may take an adjustment to recognize the clusters of melanocytes, Dr. Langley said. "You have to retrain your eye to look differently—you are looking from above. Also, it is in black and white, not color, like we're used to."

Indicative of the growing interest in this technology is the formation of the International Confocal Microscopy Working Group, launched at the February 2008 American Academy of Dermatology annual meeting in San Antonio. The group aims to form an international network of medical professionals working with confocal laser microscopy and to promote education, training, and additional research about the technology.

New software for microscopy also emerged in the past year (Electronic Zoom, Lucid Inc.). The video-capture software allows dermatologists or dermatopathologists to map a lesion and tag an area of interest. "You start with a macro image and, if you see an area you want to focus on, the software can be engaged," Dr. Langley said.

Another advance is the availability of a hand-held confocal microscopy device (VivaScope 3000, Lucid). Dr. Langley had no relevant financial disclosures.

A hand-held confocal microscopy device is one recent dermoscopy advancement. ©Lucid, Inc.

MONTREAL — Formation of an international confocal microscopy group, software that aids the detection and mapping of skin lesions, and introduction of a handheld device are among recent advances to aid in the diagnosis of lentigo maligna and other lesions in real time.

Researchers hope widespread adoption of confocal laser microscopy progress will permit further early diagnoses of cutaneous melanoma and other lesions at the bedside. "It is critical to do biopsies early. If you believe cancer starts from a single cell, you can diagnose it early [with confocal laser microscopy]. That is what we are working on now," Dr. Richard Langley said.

Described as a "living skin biopsy" by some, microscopy is not new. Pathologists have employed the intensely focused light to examine tissue specimens since the 1950s, he said. There is a limitation in live patients, however. "We cannot go through a patient's skin, so we deal with reflective light. We still have confocal concepts, but we have real-time results," Dr. Langley said at the annual conference of the Canadian Dermatology Association.

Dr. Langley and his colleagues were the first to report use of confocal laser microscopy in a series of 40 dermatology patients with superficial melanoma (J. Am. Acad. Dermatol. 2001;45:365–76).

Others have since validated that microscopy distinguishes between malignant and benign lesions in vivo. To date, studies include more than 400 patients, said Dr. Langley of Dalhousie University, Halifax, N.S.

Last year, he and his associates published the first prospective study to compare microscopy with dermoscopy. "We decided to see if we can do a prospective, blinded, single-institution study," he said.

They assessed 125 patients with suspicious pigmented lesions using both technologies, followed by a confirmatory biopsy (Dermatology 2007;215:365–72). They detected a total of 88 melanotic nevi and 37 melanomas. "Sensitivity was higher with confocal versus dermoscopy [97% vs. 89%, respectively]. The specificity was about the same [83% vs. 84%]," Dr. Langley said. "We missed one melanoma with the confocal technology, so it was not perfect."

For dermatologists accustomed to reading cross-sectional biopsies, it may take an adjustment to recognize the clusters of melanocytes, Dr. Langley said. "You have to retrain your eye to look differently—you are looking from above. Also, it is in black and white, not color, like we're used to."

Indicative of the growing interest in this technology is the formation of the International Confocal Microscopy Working Group, launched at the February 2008 American Academy of Dermatology annual meeting in San Antonio. The group aims to form an international network of medical professionals working with confocal laser microscopy and to promote education, training, and additional research about the technology.

New software for microscopy also emerged in the past year (Electronic Zoom, Lucid Inc.). The video-capture software allows dermatologists or dermatopathologists to map a lesion and tag an area of interest. "You start with a macro image and, if you see an area you want to focus on, the software can be engaged," Dr. Langley said.

Another advance is the availability of a hand-held confocal microscopy device (VivaScope 3000, Lucid). Dr. Langley had no relevant financial disclosures.

A hand-held confocal microscopy device is one recent dermoscopy advancement. ©Lucid, Inc.

MONTREAL — Formation of an international confocal microscopy group, software that aids the detection and mapping of skin lesions, and introduction of a handheld device are among recent advances to aid in the diagnosis of lentigo maligna and other lesions in real time.

Researchers hope widespread adoption of confocal laser microscopy progress will permit further early diagnoses of cutaneous melanoma and other lesions at the bedside. "It is critical to do biopsies early. If you believe cancer starts from a single cell, you can diagnose it early [with confocal laser microscopy]. That is what we are working on now," Dr. Richard Langley said.

Described as a "living skin biopsy" by some, microscopy is not new. Pathologists have employed the intensely focused light to examine tissue specimens since the 1950s, he said. There is a limitation in live patients, however. "We cannot go through a patient's skin, so we deal with reflective light. We still have confocal concepts, but we have real-time results," Dr. Langley said at the annual conference of the Canadian Dermatology Association.

Dr. Langley and his colleagues were the first to report use of confocal laser microscopy in a series of 40 dermatology patients with superficial melanoma (J. Am. Acad. Dermatol. 2001;45:365–76).

Others have since validated that microscopy distinguishes between malignant and benign lesions in vivo. To date, studies include more than 400 patients, said Dr. Langley of Dalhousie University, Halifax, N.S.

Last year, he and his associates published the first prospective study to compare microscopy with dermoscopy. "We decided to see if we can do a prospective, blinded, single-institution study," he said.

They assessed 125 patients with suspicious pigmented lesions using both technologies, followed by a confirmatory biopsy (Dermatology 2007;215:365–72). They detected a total of 88 melanotic nevi and 37 melanomas. "Sensitivity was higher with confocal versus dermoscopy [97% vs. 89%, respectively]. The specificity was about the same [83% vs. 84%]," Dr. Langley said. "We missed one melanoma with the confocal technology, so it was not perfect."

For dermatologists accustomed to reading cross-sectional biopsies, it may take an adjustment to recognize the clusters of melanocytes, Dr. Langley said. "You have to retrain your eye to look differently—you are looking from above. Also, it is in black and white, not color, like we're used to."

Indicative of the growing interest in this technology is the formation of the International Confocal Microscopy Working Group, launched at the February 2008 American Academy of Dermatology annual meeting in San Antonio. The group aims to form an international network of medical professionals working with confocal laser microscopy and to promote education, training, and additional research about the technology.

New software for microscopy also emerged in the past year (Electronic Zoom, Lucid Inc.). The video-capture software allows dermatologists or dermatopathologists to map a lesion and tag an area of interest. "You start with a macro image and, if you see an area you want to focus on, the software can be engaged," Dr. Langley said.

Another advance is the availability of a hand-held confocal microscopy device (VivaScope 3000, Lucid). Dr. Langley had no relevant financial disclosures.

A hand-held confocal microscopy device is one recent dermoscopy advancement. ©Lucid, Inc.