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Open AccessArticle

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

1
Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, 50-556 Wroclaw, Poland
2
Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
3
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
4
Department of Pathology, Wakayama Medical University, Wakayama 641-8510, Japan
5
Department of Pathology, Poznan University Medical Sciences and Greater Poland Cancer Center, 61-701 Poznan, Poland
6
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
7
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
8
Department of Dermatology, Melanoma Unit, Hospital Clínic de Barcelona, IDIBAPS, and Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, 08036 Barcelona, Spain
9
Department of Pathology, Hospital Universitari Germans Trias i Pujol, Hospital Universitari General de Catalunya, Grupo QuironSalud, Universitat Internacional de Catalunya, 08916 Barcelona, Spain
10
Department of Medicine, Section of Dermatology University of Chicago, IL 60637, USA
11
Department of Pathology, Medical University of Gdansk, 80-210 Gdansk, Poland
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Department of Tumor Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, 31-115 Crakow Branch, Poland
13
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(5), 1135; https://doi.org/10.3390/cells9051135
Received: 15 April 2020 / Revised: 29 April 2020 / Accepted: 2 May 2020 / Published: 5 May 2020
(This article belongs to the Special Issue Molecular Role of PARP in Health and Disease 2020)
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. View Full-Text
Keywords: mucosal melanoma; vulvar melanoma; sinonasal melanoma; anorectal melanoma; PARP; IDO1; prognosis; neoplasia mucosal melanoma; vulvar melanoma; sinonasal melanoma; anorectal melanoma; PARP; IDO1; prognosis; neoplasia
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Donizy, P.; Wu, C.-L.; Mull, J.; Fujimoto, M.; Chłopik, A.; Peng, Y.; Shalin, S.C.; Selim, M.A.; Puig, S.; Fernandez-Figueras, M.-T.; Shea, C.R.; Biernat, W.; Ryś, J.; Marszalek, A.; Hoang, M.P. Up-Regulation of PARP1 Expression Significantly Correlated with Poor Survival in Mucosal Melanomas. Cells 2020, 9, 1135.

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