Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens in serous ovarian neoplasms

Purpose: The cancer-testis (CT) family of antigens is expressed in a variety of malignant neoplasms and is silent in normal tissues, except for the testis. Expression of two members of this family, MAGE-A4 and NY-ESO-1, has been described in melanomas, germ cell tumors, certain carcinomas and sarcomas, and more recently in uterine neoplasms. The objective of this study was to evaluate the extent and prognostic significance of CT antigen expression in ovarian serous neoplasms. Experimental Design: Seventy-four patients with ovarian neoplasms, including 10 with serous cystadenomas, 11 with serous tumors of borderline malignancy, and 53 with serous carcinomas, were studied. Immunohistochemistry was performed with the 57B monoclonal antibody, which recognizes predominantly the MAGE-A4 antigen and the D8.38 antibody that recognizes NY-ESO-1. Results: MAGE-A4 expression was found to be present in 57% of the serous carcinomas and only in 9% of the serous tumors of borderline malignancy. No staining was detected in serous cystadenomas or in the normal ovary. In 8 of 30 positively stained serous carcinomas, >50% of the tumor cells expressed MAGE-A4. NY-ESO-1 expression was seen in 19% of the serous carcinomas, whereas serous tumors of borderline malignancy and cystadenomas were negative. A significant inverse correlation was found between MAGE-A4 expression and patient survival (P = 0.016). Multivariate analysis revealed that both tumor stage and MAGE-A4 expression were independent predictors of patient survival (P = 0.022 and P = 0.013, respectively). Conclusions: Cancer-testis antigen expression in ovarian serous neoplasms correlates directly with their degree of malignancy. MAGE-A4 expression, and to a lesser degree NY-ESO-1 expression, is characteristic of the majority of serous carcinomas. Determining the degree of MAGE-A4 expression in these tumors may provide important prognostic information. Finally, MAGE-A4 may represent a novel target for immunotherapy in serous ovarian neoplasms.