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Introduction: In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumour and sentinel-node biopsy. The objective of this study is to analyse the prognostic implications of this delay., Patients and Method: This was an observational, retrospective, cohort study in four tertiary referral hospitals. A total of 1963 patients were included. The factor of interest was the interval between the date of the excisional biopsy of the primary melanoma and the date of the sentinel-node biopsy (delay time) in the prognosis. The primary outcome was melanoma-specific survival and disease-free survival., Results: A delay time of 40 days or less (hazard ratio (HR), 1.7; confidence interval (CI), 1.2-2.5) increased Breslow thickness (Breslow ⩾ 2 mm, HR, > 3.7; CI, 1.4-10.7), ulceration (HR, 1.6; CI, 1.1-2.3), sentinel-node metastasis (HR, 2.9; CI, 1.9-4.2), and primary melanoma localised in the head or neck were independently associated with worse melanoma-specific survival (all P < 0.03). The stratified analysis showed that the effect of delay time was at the expense of the patients with a negative sentinel-node biopsy and without regression., Conclusion: Early sentinel-node biopsy is associated with worse survival in patients with cutaneous melanoma., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The G101W founder mutation is the most common CDKN2A mutation in Italy, Spain, and France. As the background of modifying genes, environmental exposures, and sun behavior vary across countries, studying G101W carriers from distinct countries offers a unique opportunity to evaluate possible modifying factors in melanoma development. We evaluated 76 G101W cases and 59 carrier controls from France, Italy, Spain, and the United States. Hair color and dysplastic nevi distributions differed significantly in cases and controls across the 4 study groups. Cases also varied significantly for eye color, freckling, and nevi. The distribution of MC1R variants in cases differed significantly across study groups because 12% of Italian melanoma patients had > or =2 MC1R variants vs. >50% for the other case groups. Several MC1R covariates showed significant associations with melanoma risk in all groups combined and in the American, French, and Spanish samples; no significant findings were observed in the Italian sample. In multiple-case families, the number and type of MC1R variants varied significantly between multiple-primary-melanoma and single-primary-melanoma patients from the 4 groups; there was also a significant decrease in median age at melanoma diagnosis as the number or type of MC1R variants increased. The variation in the effects of the cutaneous phenotypic and MC1R factors across the study sample suggests that these factors differentially contribute to development of melanoma even on a common genetic background of a germline CDKN2A mutation. Differences in melanoma risk across geographic regions justify the need for individual studies in each country before counseling should be considered.