Dopachrome tautomerase (DCT) and
tyrosinase (Tyr) are melanogenic
enzymes and structurally related melanosomal
proteins. The present study investigates DCT expression comparatively with Tyr, the most tested
melanoma biomarker, aiming to evaluate DCT potential in the assessment of melanocytic
tumors and gain insights into the molecular and pathological characterization of DCT-phenotype in
tumor progression. DCT and Tyr are simultaneously analyzed in
melanoma cell lines by semiquantitative RT-PCR, western blot, and N-
glycan analysis, and in cell populations of melanocytic
tumors by immunohistofluorescence using a novel anti-hDCT antibody against an extended sequence within DCT
luminal domain. DCT, unlike Tyr, is fully processed along the secretory pathway in both pigmented and
amelanotic melanoma cells. In 53
nevi and 116 primary
malignant melanomas, 81% and 52%, respectively, are DCT+/Tyr+, showing that DCT is a stable
antigen, retained by most
tumors and partially expressed in Tyr-negative cell populations. The DCT/Tyr disjunction is a process correlated with melanocyte neoplastic transformation and malignant progression. A
tumor architecture--DCT-phenotype-containing DCT+/Tyr- cell populations selected into the innermost dermis from double-positive cells is detected in 35% of DCT+/Tyr+ specimens. The DCT-phenotype is associated with enhanced
neurotization in benign
nevi and with ulceration in thin
malignant melanomas. The intradermal DCT+/Tyr- clones in superficial
melanomas acquire the expression and specific subcellular distribution of unfavorable prognostic markers. DCT assessment shows specific
antigen patterns with potential significance in the outcome of melanocytic lesions, connecting DCT, a mediator of a
melanoma stress-resistant pathway, and an antiapoptotic molecule to DCT- phenotypes that are possibly more stable and stress resistant.