Immunophenotypic p14 and p16 correlations with CDKN2A mutations in primary multiple and familial melanoma: An observational study

Melanoma represents an aggressive malignant tumor, encapsulating frequent loss of differentiation markers, with familial melanoma constituting a relatively commonly encountered entity, in direct relationship with cyclin-dependent kinase inhibitor 2A (CDKN2A). The present study aims to identify the association between the immunohistochemical p14-p16 profile, the molecular CDKN2A findings and clinically diagnosed familial or multiple primary melanomas (MPM). We conducted a 5-year retrospective cross-sectional study, on patients diagnosed with familial or MPM. P14 and p16 immunohistochemical staining has been applied on the selected surgical specimens simultaneously with the performance of fluorescence in situ hybridization (FISH) CDKN2A testing. 13 out of the 23 included cases displayed p14 and/or p16 immunohistochemical absence and the main positive relationships were encountered between CDKN2A homozygous deletion and p14 +/- p16 negative immunoreactions. Cases with exclusive p16 absent reaction (n = 7) were more frequently associated with the presence of distant metastases (85.71%), while samples with exclusive p14 immunohistochemical loss exhibited more favorable histopathological prognostic markers. The average percentage of p16-stained nuclei in the superficial dermis and the deep dermis were equal (29.54% for each), therefore infirming its potential predictive and/or prognostic utility. The present study is the first of its type to approach the clinical, evolutionary and immunophenotypic correlations between p14-p16 immunohistochemical testing, CDKN2A molecular biology pattern, familial melanoma and spontaneous MPM in a cohort of Romanian patients. This analysis highlighted the value of singular p16 immunohistochemical absence as a predictor for aggressive biological behavior and unfavorable prognosis in familial melanoma and/or MPM, in comparison with the exclusive loss of p14, indifferent to the histopathological subtype. The present study emphasizes the utility of immunohistochemistry as a less expensive method of complementing the current testing arsenal and could represent the starting point for the elaboration of tailored diagnostic and therapeutic algorithms, based on the discovered p14-p16-CDKN2A significant correlation.