Histologic, molecular, and epidemiologic data suggest that cutaneous
melanomas arise through diverse causal pathways, one of which appears mediated by chronic sunlight exposure, and another associated with a
nevus-prone phenotype. To further explore etiologic heterogeneity, we compared expression of key
melanoma-related
proteins according to histologic characteristics of the
tumors and epidemiologic risk factors among a sample of 129 patients newly diagnosed with
melanoma.
Tumor tissue was stained with
antibodies to phospho-
mitogen-activated protein kinase (P-MAPK), Brn-2,
retinoblastoma protein (pRb), p53, and p16. Using logistic regression analysis, we estimated the odds ratio (OR) and 95% confidence interval (95% CI) of
protein expression associated with factors of interest. Except for pRb, candidate
protein expression was detected in fewer than half the
melanomas examined (P-MAPK, 39%; Brn-2, 30%; p53, 24%; p16, 41%). Strong pRb expression was associated with the presence of >20 solar
keratoses (OR 6.5, 95% CI: 1.7-25.1) and
melanomas with marked to moderate solar elastosis. p53 expression was positively associated with skin that readily burned (OR 3.8, 95% CI: 0.8-19.0) and was inversely associated with >60
nevi (OR 0.3, 95% CI: 0.04-1.5).
Melanomas expressing P-MAPK were more likely to have contiguous neval remnants (OR 2.7, 95% CI: 1.1-6.5). P-MAPK and Brn-2 immunopositive
melanomas were >/=4-fold more likely to be of the superficial spreading subtype. Brn-2 and p16 immunopositive
melanomas had a greater Breslow thickness than
melanomas that did not express these
proteins. Brn-2, pRb, and p16
proteins were consistently coexpressed. These findings support the hypothesis that molecular profiles of
melanoma reflect their histologic and epidemiologic characteristics, offering further evidence of more than one
melanoma causal pathway. Exactly how the expression of each
protein relates to the causal pathways needs to be further explored.