Prostate-specific Membrane Antigen (PSMA) Expression in the Neovasculature of Gynecologic Malignancies: Implications for PSMA-targeted Therapy

Abstract

The goal of the study was to examine expression of prostate-specific membrane antigen (PSMA) in neovasculature of gynecologic cancers, as PSMA-targeted therapy has showed a promise in treatment of advanced carcinomas. The study included cervical carcinoma (n=28), vulvar carcinoma (n=20), endometrial carcinoma (n=23), primary ovarian carcinoma (n=21), metastatic ovarian carcinoma (n=25), and normal cervix (n=12) as negative control. All cases were immunostained using anti-CD31 antibody to delineate capillary endothelial cells. In parallel, all cases were immunostained using anti-PSMA antibody. The PSMA staining was assessed in tumor capillaries and in normal tissues and scored as a percentage of CD31 staining. PSMA expression was found in the tumor neovasculature, and no significant expression was identified in vasculature of normal tissues. The extent of PSMA staining in tumor capillaries varied from high expression in ovarian and endometrial cancers, to medium expression in cervical squamous cell carcinomas, and low expression in cervical adenocarcinomas and vulvar cancers. All (100%) cases of primary ovarian carcinoma, ovarian carcinoma metastases, and primary endometrial carcinoma showed PSMA expression in tumor vasculature, which was diffuse in majority of cases. The expression of PSMA in ovarian cancer metastases was similar among different metastatic foci of the same tumor. Fifteen percent of cervical squamous cell carcinoma, 50% of cervical adenocarcinoma, and 75% of vulvar carcinomas showed no capillary expression of PSMA. In conclusion, PSMA is highly and specifically expressed in the neovasculature of ovarian, endometrial, and cervical squamous carcinoma, rendering it a potential therapeutic vascular target.