Frequent Glypican-3 Overexpression in Ovarian Clear Cell Adenocarcinoma
D Maeda, S Ota, Y Takazawa, H Aburatani, S Nakagawa, M Fukayama. Fuculty of Medicine, the University of Tokyo, Tokyo, Japan; Research Center for Advanced Science and Technology, the University of Tokyo, Tokyo, Japan; Faculty of Medicine, the University of Tokyo, Tokyo, Japan
Background: Glypican-3 (GPC3) is a heparan sulfate proteoglycan that is overexpressed in hepatocellular carcinoma, malignant melanoma, and testicular yolk sac tumor (YST). GPC3 is also known as a tumor marker and potential target for immunotherapy. There have been relatively few studies regarding GPC3 expression in ovarian carcinoma, the results of which were inconsistent, especially with regard to ovarian clear cell adenocarcinoma (CCA).
Design: We used immunohistochemistry to evaluate GPC3 expression in 213 ovarian adenocarcinomas, including a large number of CCAs (n=94). In addition, GPC3 expression in ovarian surface epithelial inclusions, endometriosis, and other Mllerian duct derivatives, such as the fallopian tube epithelium, endometrial epithelium, and endocervical epithelium, were investigated. To determine the value of GPC3 immunostaining in distinguishing ovarian CCAs from YSTs, immunostaining was also performed in 6 YSTs.
Results: Among the four major histological subtypes of ovarian adenocarcinoma (clear cell, mucinous, endometrioid, and serous), GPC3 expression was detected in a significantly high proportion of CCAs (44%, P<0.0001). In contrast, positive immunoreactivity for GPC3 was rarely observed in other histological subtypes of ovarian adenocarcinoma: 4%, 5%, and 11% in mucinous, endometrioid, and serous adenocarcinomas, respectively. Ovarian surface epithelial inclusions and benign Mllerian duct derivatives were usually negative for GPC3. All 6 ovarian YSTs showed diffuse immunoreactivity for GPC3. In CCA cases, no correlation was observed between GPC3 expression and clinicopathological factors, such as tumor stage, lymph node metastasis, peritoneal dissemination, and mortality rate. However, when limited to stage III/IV CCA cases, GPC3 positivity was associated with poor overall survival (P=0.019).
Conclusions: We showed frequent GPC3 overexpression in ovarian CCAs. As ovarian CCA is known for its resistance to conventional chemotherapy, our results suggest that GPC3 may be a useful alternative target for immunotherapy in advanced stage CCA. For surgical pathologists, it is important to know that GPC3 immunohistochemistry is of limited value in discriminating between ovarian CCA and YST.
Monday, March 9, 2009 2:30 PM
Platform Session: Section C, Monday Afternoon