The emerging role of dual specificity phosphatase 3 in melanocytic cancer: from oncogenesis to clinical value.

Background: Dual specificity phosphatase 3 (DUSP3) participates in various cancers, whereas its involvement in melanocytic oncogenesis needs to be identified.

Methods: One hundred seventy-two biopsied lesions were immunohistochemically stained for DUSP3, divided in 4 groups: common nevi (CN), dysplastic nevi (DN), nevus and melanoma components of nevus-associated melanomas (N-NAMs and M-NAMs, respectively). Positivity was based on the numerical and categorical Immunoreactive Score after evaluation of staining's intensity and proportion.

Results: A decrease of DUSP3 positivity was observed along the 4 groups (mean [SD] numerical IRS scores: CN: 7.5 [3.5]; DN: 6.2 [3.6]; 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. Paired analysis of the 84 matched NAM cases underscored a downgrade in positivity of M-NAM vs. N-NAM per tumor (Wilcoxon Signed-Rank Test: P<0.001). Multivariate analysis revealed that probability of any nevus diagnosis against M-NAM was increased 3-11 times (adjusted OR CN vs. M-NAM: 11.333, 95% CI: 2.995-42.876; adjusted OR DN vs. M-NAM: 6.495, 95% CI: 2.496-16.900; OR N-NAM vs. M-NAM: 3.225, 95% CI: 1.745-5.961. P<0.001).

Conclusions: DUSP3 seems to act as a tumor-suppressor, and its depletion seems to contribute to the progression of NAM. This is the first study validating DUSP3's association with melanocytic neoplasms, improving the understanding of their oncogenesis and diagnostics. Additional studies are required for clarifying its utility in the clinical setting.