The eighth edition of the American Joint Committee on Cancer (AJCC) staging system has been effective since January 2018.,It has introduced some major changes in the localized/locoregional melanoma classification.,However, it has not been demonstrated how this classification was validated on external, clinical data.,In this retrospective study, we have included 2474 patients diagnosed with cutaneous melanoma in localized or locoregional stage.,They were treated surgically in our Center between years 1998 and 2014.,Melanoma-specific and overall survival were calculated for each stage according to TNM7 and TNM8 using Kaplan-Meier estimator.,The melanoma-specific survival rates in our patients were similar to those reported from original cohort used to build TNM8 classification except for stage IIIC (5-year melanoma-specific survival 44.6% vs 51.8%, respectively for TNM7 vs TNM8).,Our study validated the eighth edition of TNM melanoma staging system as a viable tool in prognosis of the long-term survival of patients with localized or locoregionally advanced melanoma on an independent cohort.,The new TNM 8 system has brought important improvements in prognostic assessment for melanoma patients.,Deeper understanding of the significance of satellite/in-transit lesions may be required.,The online version of this article (10.1186/s12957-019-1669-6) contains supplementary material, which is available to authorized users.
The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis.,This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM.,Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients.,Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles.,Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm.,The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses.,Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients.,Patients with a “favorable” methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis.,Median OS of stage IIIC patients with a “favorable” vs. “unfavorable” methylation profile were 31.5 and 10.4 months, respectively.,The 5 year OS for stage IIIC patients with a “favorable” methylation profile was 41.2% as compared to 0% for patients with an “unfavorable” methylation profile.,Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for “unfavorable” methylation profile; 95% Confidence Interval: 1.02-5.70; P = 0.045).,A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified.,A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients.,Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients.