IMMUNOHISTOCHEMICAL EXPRESSION OF DUSP3 IN NEVUS-ASSOCIATED MELANOMAS

INTRODUCTION: Dual Specificity Phosphatase 3 (DUSP3) seems to participate in various cancers, with both tumor suppressing and promoting properties reported in melanoma. METHODS: 42 biopsied NAMs from 42 individuals were collected for immunohistochemical staining. The nevus and melanoma compounds were evaluated separately per tumor. Positivity was based on the numerical and categorical Immunoreactive Score after evaluation of staining’s intensity and proportion. OBJECTIVES: This study’s objective is to investigate DUSP3’s immunohistochemical expression among nevus-associated melanomas (NAMs) and thus its potential involvement in melanocytic oncogenesis from the standpoint of its post-translational levels. RESULTS: A general decrease of DUSP3’s positivity was observed in M-NAMs compared to N-NAMs [mean(SD) numerical IRS scores: N-NAMs: 4.0(2.9); M-NAMs: 1.9(1.1), p<0.001]. Remarkably, no strongly positive M-NAMs were observed while 21.4% of them developed from a negative nevus. Furthermore, paired analysis of the 84 matched NAM cases underscored a downgrade in DUSP3 positivity of M-NAM vs N-NAM per tumor (Wilcoxon signed-rank test: p<0.001). Univariate analysis revealed significant association when comparing N-NAMs with M-NAMs. Specifically, probability of N-NAM diagnosis against M-NAM was increased approximately 3 times (OR N-NAM vs M-NAM: 3.225, 95% CI: 1.745-5.961. p<0.001) per 1 unit increase of the categorical IRS score. CONCLUSION: Our findings highlight that poor DUSP3’s positivity and even more DUSP3’s negativity -therefore loss of DUSP3’s expression- are more likely associated with melanocytic malignancy. This is the first study rigorously examining DUSP3’s immunohistochemical expression in NAMs, contributing to the improved understanding of their oncogenesis and diagnostics.