Current staging guidelines are insufficient to predict which patients with thin primary melanoma are at high risk of recurrence. Computer-assisted image analysis may allow for more practical and objective histopathological analysis of primary tumors than traditional light microscopy. We studied a prospective cohort of stage IB melanoma patients treated at NYU Langone Medical Center from 2002–2014. Primary tumor width, manual area, digital area, and conformation were evaluated in a patient subset via computer-assisted image analysis. The associations between histologic variables and survival were evaluated using Cox proportional hazards model. Logistic regressions were used to build a classifier with clinicopathological characteristics to predict recurrence status. Of the 655 patients with stage IB melanoma studied, a subset of 149 patient tumors (63 recurred, 86 did not recur) underwent computer-assisted histopathological analysis. Increasing tumor width (HR 1.17, p=0.01) and digital area (HR 1.08, p<0.01) were significantly associated with worse recurrence-free survival, while non-contiguous conformation (HR 0.57, p=0.05) was significantly associated with better recurrence-free survival. The novel histopathological classifier composed of digital area, conformation, and baseline variables effectively distinguished recurrent cases from nonrecurrent cases (AUC 0.733, 95% CI 0.647–0.818), compared to the baseline classifier alone (AUC 0.635, 95% CI 0.545–0.724). Primary tumor cross-sectional area, width, and conformation measured via computer-assisted analysis may help identify high-risk patients with stage IB melanoma.
The extent of PTEN loss that confers clinical and biological impact in melanoma is unclear. We evaluated the clinical and biologic relevance of PTEN dosage in melanoma and tested the postulate that partial PTEN loss is due to epigenetic mechanisms. PTEN expression was assessed by immunohistochemistry in a stage III melanoma cohort (n = 190) with prospective follow up. Overall, 21 of 190 (11%) tumors had strong PTEN expression, 51 of 190 (27%) had intermediate PTEN, 44 of 190 (23%) had weak PTEN, and 74 of 190 (39%) had absent PTEN. Both weak and absent PTEN expression predicted shorter survival in multivariate analyses (hazard ratio = 2.13, P < 0.01). We show a continuous negative correlation between PTEN and activated Akt in melanoma cells with titrated PTEN expression and in two additional independent tumor datasets. PTEN genomic alterations (deletion, mutation), promoter methylation, and protein destabilization did not fully explain PTEN loss in melanoma, whereas PTEN levels increased with treatment of melanoma cells with the histone deacetylase inhibitor LBH589. Our data indicate that partial PTEN loss is due to modifiable epigenetic mechanisms and drives Akt activation and worse prognosis, suggesting a potential approach to improve the clinical outcome for a subset of patients with advanced melanoma.
To understand the role that tattooists play in providing skin care advice, we conducted an online, survey-based study of 90 licensed tattooists in New York City. The survey asked tattooists about their exposure to adverse tattoo events, advising on tattoo removal/correction, behaviors regarding preexisting skin conditions and aftercare, confidence in addressing client questions about adverse events and preexisting conditions, and prior training about skin conditions related to tattoos. Most tattooists (92.8%) reported being asked by clients to evaluate adverse tattoo reactions, 85% were asked about tattoo removal, and 90% were asked about the safety of getting a tattoo with a preexisting skin condition. About half (56.1%) had received training about skin conditions related to tattoos. Tattooists with prior training reported higher rates of optimal skin care behaviors and higher confidence with tattoo-related skin conditions; 91.4% reported interest in skin care education. Tattooists play a major role in the skin health of their clients. Providing education for tattooists may improve skin care in populations less likely to see a dermatologist.
We identify Ki-67 and ln (thickness) as potential biomarkers for patients with thick melanoma who have undergone nodal staging. If validated in additional studies, these biomarkers could be integrated into the staging criteria to improve risk-stratification.
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