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Hum Pathol. 2018 Nov 14. pii: S0046-8177(18)30427-1. doi: 10.1016/j.humpath.2018.10.028. [Epub ahead of print]

Immunohistochemistry expression of targeted therapies biomarkers in ovarian clear cell and endometrioid carcinomas (type I) and endometriosis.

Author information

1
Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil. Electronic address: dr.abarreta@gmail.com.
2
Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
3
Postgraduate Program in Medical Sciences, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
4
Department of Pathology, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
5
Faculty of Pharmacy, University of Campinas, Campinas, São Paulo, Brazil.

Abstract

Ovarian clear cell and endometrioid carcinomas (Type I) are thought to develop from endometriosis. ARID1A loss of expression is known to be related to the promotion of the endometriosis carcinogenesis. Despite the diverse origins and prognosis of Type I and Type II carcinomas, surgery followed by platinum-based chemotherapy is the mainstay of treatment for both. Limited knowledge about the expression of targeted therapies' biomarkers prevents the use of such markers as potential guides for tailored treatment. This study aimed to evaluate the expression of ARID1A gene and target therapies biomarkers (VEGF, PD-L1, and PARP-1) in ovarian clear cell and endometrioid carcinomas and endometriosis, and its relationship with prognosis. Forty-six ovarian clear-cell and endometrioid carcinomas, and 24 endometriosis foci samples retrieved from the same surgical specimens were studied. ARID1A, VEGF, PD-L1, and PARP-1 immunohistochemistry (IHC) expression was compared in carcinomas and endometriosis with regard to the clinicopathological features and prognosis. We found that endometriosis was associated with increased rates of diagnosis of cancer in the initial stages (P=.008). Different levels of expression of all biomarkers were detected in clear-cell and endometrioid carcinomas and endometriosis. However, only the VEGF expression level showed a significant increase in the carcinoma group when compared with endometriosis (P=.0002). PARP-1 overexpression correlated with worse progression-free survival (P=.03) and overall survival (P=.01). In conclusion, endometriosis and ovarian clear-cell and endometrioid carcinomas exhibited ARID1A loss of expression, and VEGF, PD-L1, and PARP-1 expression. PARP-1 overexpression in clear-cell and endometrioid carcinomas was associated with early recurrence and worse overall survival.

KEYWORDS:

Clear Cell Ovarian Cancer; Endometrioid Ovarian Cancer; Poly (ADP-Ribose) Polymerase; Programmed Cell Death Receptor 1; Vascular Endothelial Growth Factor

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