PMID- 24709887 OWN - NLM STAT- MEDLINE DCOM- 20141228 LR - 20191210 IS - 1473-5636 (Electronic) IS - 0960-8931 (Linking) VI - 24 IP - 3 DP - 2014 Jun TI - Value of dopachrome tautomerase detection in the assessment of melanocytic tumors. PG - 219-36 LID - 10.1097/CMR.0000000000000066 [doi] AB - 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. FAU - Filimon, Anca AU - Filimon A AD - Departments of aMolecular Cell Biology bBioinformatics and Structural Biochemistry, Institute of Biochemistry, Romanian Academy cDepartment of Pathology, Colentina University Hospital, Bucharest, Romania. FAU - Zurac, Sabina A AU - Zurac SA FAU - Milac, Adina L AU - Milac AL FAU - Sima, Livia E AU - Sima LE FAU - Petrescu, Stefana M AU - Petrescu SM FAU - Negroiu, Gabriela AU - Negroiu G LA - eng PT - Comparative Study PT - Evaluation Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Melanoma Res JT - Melanoma research JID - 9109623 RN - 0 (Biomarkers, Tumor) RN - EC 1.14.18.1 (Monophenol Monooxygenase) RN - EC 5.3.- (Intramolecular Oxidoreductases) RN - EC 5.3.3.12 (dopachrome isomerase) SB - IM MH - Biomarkers, Tumor/genetics/*metabolism MH - Fluorescent Antibody Technique MH - Gene Expression Regulation, Enzymologic MH - Gene Expression Regulation, Neoplastic MH - HEK293 Cells MH - HeLa Cells MH - Humans MH - Intramolecular Oxidoreductases/genetics/*metabolism MH - Melanocytes/*enzymology/pathology MH - Melanoma/*enzymology/genetics/pathology MH - Monophenol Monooxygenase/metabolism MH - Nevus, Pigmented/*enzymology/genetics/pathology MH - Phenotype MH - Predictive Value of Tests MH - Prognosis MH - RNA Interference MH - Skin Neoplasms/*enzymology/genetics/pathology MH - Transfection EDAT- 2014/04/09 06:00 MHDA- 2014/12/30 06:00 CRDT- 2014/04/09 06:00 PHST- 2014/04/09 06:00 [entrez] PHST- 2014/04/09 06:00 [pubmed] PHST- 2014/12/30 06:00 [medline] AID - 10.1097/CMR.0000000000000066 [doi] PST - ppublish SO - Melanoma Res. 2014 Jun;24(3):219-36. doi: 10.1097/CMR.0000000000000066.