Glypican-3 expression in clear cell adenocarcinoma of the ovary

Glypican-3 is a heparan sulfate proteoglycan that is overexpressed in various neoplasms such as hepatocellular carcinoma, malignant melanoma, and testicular yolk sac tumor. Glypican-3 is currently regarded as a tumor marker and potential target for immunotherapy. To clarify the significance of glypican-3 expression in ovarian clear cell adenocarcinoma, we evaluated glypican-3 expression by immunohistochemistry in nonneoplastic and neoplastic ovaries, and other Müllerian duct derivatives including endometrium in different menstrual phases. Among the benign lesions examined, glypican-3 expression was identified exclusively in the endometrial epithelium in the gestational period. A total of 213 cases of ovarian adenocarcinoma, including 94 clear cell adenocarcinomas, were studied. Glypican-3 expression was observed in 44% of clear cell adenocarcinomas, whereas it was rarely observed in other histological subtypes: mucinous (4%), endometrioid (5%), and serous (11%; P<0.0001). All six ovarian yolk sac tumors showed diffuse immunoreactivity for glypican-3. In cases of clear cell adenocarcinoma, no correlations were found between glypican-3 expression and clinicopathological factors, such as tumor stage, lymph node metastasis, peritoneal dissemination, and death rate. However, glypican-3 expression was significantly associated with poor overall survival in stage III/IV clear cell adenocarcinoma cases. Our results suggest that overexpression of glypican-3 may be related to the development and aggressive behavior of ovarian clear cell adenocarcinoma.