Glypican-3 expression in clear cell adenocarcinoma of the ovary

Abstract

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 Mü llerian 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%; Po0.0001). 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.

Napsin A is a specific marker for ovarian clear cell adenocarcinoma

“…32,33 However, one study reported HNF1b positivity in the nuclei of normal and tumor cells in the endometrium, 34 and the establishment of other markers may also be useful for differential diagnosis of clear cell adenocarcinoma. Annexin-A4, 35,36 HOXA10, 37 phospho-serine aminotransferase, 36 and glypican 3 38 are all suitable candidates. A recent study has shown that a certain proportion of papillary serous adenocarcinoma also exhibits Annexin-A4 expression related to chemoresistance, 39 and the expression of HOXA10 or glypican 3 is less frequently associated with poor outcome.…”

“…A recent study has shown that a certain proportion of papillary serous adenocarcinoma also exhibits Annexin-A4 expression related to chemoresistance, 39 and the expression of HOXA10 or glypican 3 is less frequently associated with poor outcome. 37,38,40 Glypican 3 is also known to be expressed in yolk sac tumors of the ovary. 38 In this study, all of the 93 primary ovarian surface epithelial tumors that were not of the clear cell subtype and three cases of yolk sac tumors were all negative for napsin A staining, with the exception of focal (o10% area) staining of serous and endometrioid adenocarcinoma cases with clear cell-or hob-nail changes resembling clear cell adenocarcinoma.…”

“…37,38,40 Glypican 3 is also known to be expressed in yolk sac tumors of the ovary. 38 In this study, all of the 93 primary ovarian surface epithelial tumors that were not of the clear cell subtype and three cases of yolk sac tumors were all negative for napsin A staining, with the exception of focal (o10% area) staining of serous and endometrioid adenocarcinoma cases with clear cell-or hob-nail changes resembling clear cell adenocarcinoma. Thus, we consider napsin A to be another suitable marker to specifically distinguish clear cell adenocarcinoma from other ovarian tumors with a relatively high sensitivity.…”

The Utility of Immunohistochemistry in the Differential Diagnosis of Gynecologic Disorders

“…167,184,185 GP-3 positive staining in yolk sac tumor and negative staining in embryonal carcinoma is used as an additional marker in differentiating these 2 tumors. [186][187][188] It should be noted that GP-3 stains positively in choriocarcinoma and metastatic hepatocellular carcinoma and may be expressed in immature teratoma, metastatic acinar carcinoma of the pancreas, and squamous cell carcinoma of the cervix.…”

Breast and Ovarian Cancers

“…GPC3 was expressed in about 40% of clear cell carcinomas (Maeda et al 2009;Umezu et al 2010) but rare in other types such as mucinous, endometrioid, or serous (Maeda et al 2009). One study showed that glypican-3 was significantly associated with poor overall survival in stage III/IV clear cell adenocarcinoma cases (Maeda et al 2009), whereas another study showed association with poor progression-free survival in stage I clear cell carcinoma patients (Umezu et al 2010). Both studies showed no correlations between its expression and clinicopathological factors (Maeda et al 2009;Umezu et al 2010).…”