Abstract
Introduction: 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. Methods: PARP1, PD-L1 and IDO1 immunostains were performed on 192 mucosal melanomas including 86 vulvar, 89 sinonasal, and 17 anorectal melanomas. Results: By Kaplan–Meier analyses, high PARP1 expression correlated with worse overall and melanoma-specific survival (log-rank p values = 0.026 and 0.047, respectively). Tumors with combined PARP1 and IDO1 high expression correlated with worse overall and melanoma-specific survival (p = 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 (p = 0.02). High tumoral PD-L1 and IDO1 expression were associated with ulcerated primary tumors (p = 0.019, 0.0019, respectively). By linear regression analyses, correlations between PARP1 expression versus IDO1 expression (p = 0.0001) and mitotic index (p = 0.0052) were observed. Conclusion: 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.
Highlights
Mucosal melanoma is rare and associated with poorer prognosis in comparison to conventional melanoma subtypes
Due to incomplete data such as tumor size and tumor thickness in cases such as sinonasal melanomas, the patients were divided into stage
poly (ADP-ribose) polymerase 1 (PARP1) bookmarks genes determined by NFATC2, a transcriptional factor which is a crucial regulator of oncogenic transformation [9,22,23]
Summary
Mucosal melanomas encompass primary melanomas of the head and neck region (sinonasal and oral melanoma), female genital tract (vulvar and vaginal melanoma), anorectal melanoma, upper gastrointestinal tract (esophagus, stomach, intestine), and urinary tract (urethra, urinary bladder) [1]. Impaired DNA repair and the associated genomic instability is a potential effect of abnormal activity of PARP1 in neoplastic cells, driving mutagenicity, which increases neoantigen load and tumoral immunogenicity [14]. Understanding the clinical and pathologic features associated with expression of these immune markers in mucosal melanoma may provide insights into effective strategies for combination therapy. IDO1 is expressed in tumoral cells and adaptive immune response cells, and its reactivity correlates with a shorter survival in several cancers [16,17]. We investigate the prognostic role of PARP1, PD-L1, and IDO1 protein expression and explore the possible associations between tumoral PARP1, PD-L1, and IDO1 expression in a series of mucosal melanomas
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