Oncofetal Protein Glypican-3 Distinguishes Yolk Sac Tumor From Clear Cell Carcinoma of the Ovary

Department of Pathology, Stanford University, Stanford, CA 94305, USA.
American Journal of Surgical Pathology (Impact Factor: 5.15). 04/2008; 32(4):600-7. DOI: 10.1097/PAS.0b013e31815a565a
Source: PubMed


Clear cell carcinoma (CCC) of the ovary is the surface epithelial neoplasm most often confused with primitive germ cell tumors, particularly yolk sac tumor (YST) and dysgerminoma. OCT3/4 has proven to be a sensitive and relatively specific marker for the latter entity, but existing markers for YST are limited. Recent studies suggest that glypican-3 (GPC3), an oncofetal protein expressed in fetal liver and malignant tumors of hepatocytic lineage, is also expressed in germ cell tumors, particularly YST. To investigate whether GPC3 is useful in distinguishing YST from ovarian CCC, we studied the expression of GPC3 in a large series of ovarian neoplasms and compared it to the expression profiles of CK7 and alpha-fetoprotein. Tissue microarrays containing over 400 benign and malignant ovarian neoplasms, including 34 CCCs were stained with monoclonal GPC3 (clone 1G12, Biomosaics, Burlington, VT). These arrays contained a wide assortment of ovarian surface epithelial neoplasms and sex cord stromal neoplasms, as well as germ cell tumors. Full paraffin tissue sections from 32 YSTs and 10 CCCs were also assessed. All but one YST (97%), including those associated with mixed germ cell tumor were positive for GPC3, whereas all teratomas and embryonal carcinomas were negative. Both cytoplasmic and membrane staining were present in the positive cases, with no background staining. The syncytiotrophoblastic cells in the germ cell tumors and placental villi included in the arrays were also positive for GPC3. Most CCCs (83%) were completely negative for GPC3, as were 99% serous, 94% endometrioid, and 100% mucinous tumors. Five CCCs exhibited focal, moderate to strong GPC3 expression and in 2 the expression was focal and weak. All other tissues, including normal ovary were negative for GPC3. GPC3 seems to be a promising diagnostic marker for differentiating YST from ovarian CCC (P < 0.0001). Because GPC3 may be associated with alpha-fetoprotein expression, further studies are required to determine the utility of GPC3 in differentiating YST from CCC with hepatoid differentiation.

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    • "However in elderly, postmenopausal women, AFP-producing ovarian malignancies are rarely encountered and their histology varies. Some AFP-producing ovarian tumors in postmenopausal women have been documented, such as endometrioid adenocarcinoma with a yolk sac component, mucinous adenocarcinoma with a yolk sac component, CCA with a serous adenocarcinoma component, and endometrioid adenocarcinoma with a clear cell component (Abe et al., 2008; Kamoi et al., 2002; Esheba et al., 2008; Cetin et al., 2007; Maida et al., 1998). However, the ovarian tumor in our case, which was largely composed of clear cells, was different from these other tumors histopathologically in terms of lacking a YST component and forming glands similar to a gland-like fetal gut. "
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    ABSTRACT: •A 59-year-old postmenopausal woman had ovarian clear cell adenocarcinoma producing AFP.•The tumor lacked a yolk sac component and formed ducts similar to the fetal gut.
    Gynecologic Oncology Reports 04/2014; 8:24-6. DOI:10.1016/j.gynor.2014.03.001
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    • "Down regulation of GPC3 is frequently detected in ovarian carcinoma, breast cancer, and mesothelioma [7], implying GPC3 as a tumor suppressor gene in these organs. In contrast, GPC3 may act as an oncofetal protein in carcinomas of various other organs, such as hepatocellular carcinoma (HCC) [10], fibrolamellar HCC [11], germ cell tumors [12], bronchogenic squamous cell carcinoma [13], and gastric cancer, as this gene is highly expressed in tumor lesions compared with corresponding normal tissues [14]. GPC3 was found to be expressed in the majority of cases of HCC with a sensitivity ranging from 72% to 90% [15], and a specificity between 96% and 100%. "
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    ABSTRACT: Purpose Evaluation of the sensitivity and specificity of glypican3 (GPC3) in differentiating hepatocellular carcinoma (HCC) from metastatic carcinomas of the liver in cell block material. Patients and methods Sixty cell blocks were prepared from liver FNAs performed in the radiodiagnosis department, National Cancer Institute, in the period between August 2011 and May 2012. Cases diagnosed as hepatocellular carcinoma, or metastatic carcinoma were included in the study. Cell block sections were stained with anti GPC-3. Sensitivity, specificity, and positive and negative predictive values, of GPC3 were calculated. The final diagnosis was based on the triple approach of clinical data, radiological findings, as well as cytomorphologic features aided by GPC-3 results. Results 70% of cases were diagnosed as HCC, and 30% as metastatic carcinomas. 95.2% of HCC cases expressed GPC3. Poorly differentiated cases showed the highest GPC3 sensitivity (100%), followed by moderately differentiated cases (96.5%), while well differentiated cases expressed GPC3 in 90% of cases. 83.3% of metastatic carcinomas were negative for GPC3. In this study, sensitivity of GPC-3 in HCC was 95.2%, specificity was 83.3%, positive and negative predictive values were 93% and 88.2% respectively, and total accuracy was 91.7%. Conclusion Immunocytochemical staining for GPC3 in cell block material is a highly sensitive and specific method capable of distinguishing HCC from the vast majority of metastatic carcinomas of the liver.
    Journal of the Egyptian National Cancer Institute 12/2013; 25(4):173-80. DOI:10.1016/j.jnci.2013.07.004
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    • "Positive staining for this glypican was noted in a proportion of recurrent cases but not associated with chemoresponse. Clear cell carcinoma occurs more frequently in Japan than in Western countries, and two early studies with small numbers of cases yielded conflicting results regarding glyp- ican-3 expression in clear cell adenocarcinoma of the ovary (Stadlmann et al. 2007; Esheba et al. 2008). However, more recent studies focusing on clear cell carcinoma have been performed in Japan. "
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    ABSTRACT: Tumor markers are widely used in pathology not only for diagnostic purposes but also to assess the prognosis and to predict the treatment of the tumor. Because tumor marker levels may change over time, it is important to get a better understanding of the molecular changes during tumor progression. Occurrence of breast and ovarian cancer is high in older women. Common known risk factors of developing these cancers in addition to age are not having children or having children at a later age, the use of hormone replacement therapy, and mutations in certain genes. In addition, women with a history of breast cancer may also develop ovarian cancer. Here, the authors review the different tumor markers of breast and ovarian carcinoma and discuss the expression, mutations, and possible roles of cell surface heparan sulfate proteoglycans during tumorigenesis of these carcinomas. The focus is on two groups of proteoglycans, the transmembrane syndecans and the lipid-anchored glypicans. Both families of proteoglycans have been implicated in cellular responses to growth factors and morphogens, including many now associated with tumor progression.
    Journal of Histochemistry and Cytochemistry 01/2012; 60(1):9-21. DOI:10.1369/0022155411428469 · 1.96 Impact Factor
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