Up-Regulation of PARP1 Expression Significantly Correlated with Poor Survival in Mucosal Melanomas

• Published in: Cells (Basel, Switzerland) Switzerland), 2020-05, Vol.9 (5), p.1135
• Main Authors: Donizy, Piotr, Wu, Cheng-Lin, Mull, Jason, Fujimoto, Masakazu, Chłopik, Agata, Peng, Yan, Shalin, Sara C, Selim, M Angelica, Puig, Susana, Fernandez-Figueras, Maria-Teresa, Shea, Christopher R, Biernat, Wojciech, Ryś, Janusz, Marszalek, Andrzej, Hoang, Mai P
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; anorectal melanoma; B7-H1 Antigen - metabolism; Gene Expression Regulation, Neoplastic; Humans; IDO1; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Kaplan-Meier Estimate; Linear Models; Melanoma - genetics; Melanoma - pathology; Middle Aged; mucosal melanoma; Mucous Membrane - pathology; Multivariate Analysis; PARP; Poly (ADP-Ribose) Polymerase-1 - genetics; Proportional Hazards Models; sinonasal melanoma; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Survival Analysis; Ulcer - pathology; Up-Regulation - genetics; vulvar melanoma; Young Adult
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9051135

Mucosal melanoma is rare and associated with poorer prognosis in comparison to conventional melanoma subtypes. Little is known about the prognostic significance as well as possible associations between PARP1 and immunologic response in mucosal melanoma. PARP1, PD-L1 and IDO1 immunostains were performed on 192 mucosal melanomas including 86 vulvar, 89 sinonasal, and 17 anorectal melanomas. By Kaplan-Meier analyses, high PARP1 expression correlated with worse overall and melanoma-specific survival (log-rank values = 0.026 and 0.047, respectively). Tumors with combined PARP1 and IDO1 high expression correlated with worse overall and melanoma-specific survival ( = 0.015, 0.0034 respectively). By multivariate analyses, high PARP1 expression remained a predictor of worse survival independent of stage. By Fisher's exact test, high PARP1 expression correlated with highly mitogenic tumors ( = 0.02). High tumoral PD-L1 and IDO1 expression were associated with ulcerated primary tumors ( = 0.019, 0.0019, respectively). By linear regression analyses, correlations between PARP1 expression versus IDO1 expression ( = 0.0001) and mitotic index ( = 0.0052) were observed. Increased expression of PARP1 is an independent negative prognostic marker in mucosal melanomas. The association between PARP1 and IDO1 and their combined adverse prognostic role raise the potential of combined therapy in mucosal melanoma.