Glypican-3 (GPC3) is a plasma membrane-bound proteoglycan that can be overexpressed in certain malignancies but has been particularly linked to hepatocellular carcinoma (HCC). GPC3 is currently used as an immunohistochemical marker for HCC, but its expression in epithelial neoplasms of the gastrointestinal (GI) tract and pancreas, a common source of liver metastasis, has not been studied in detail. In this study, we examined GPC3 immunoreactivity in 98 neoplasms of the GI tract including 30 adenocarcinomas (ADCA), 29 squamous cell carcinomas (esophageal and anal), and 39 neuroendocrine carcinomas, and 60 neoplasms of the pancreas including 22 ADCA, 26 pancreatic neuroendocrine neoplasms, and 12 pancreatic acinar cell carcinomas. Two control groups of 32 HCCs and 16 intrahepatic cholangiocarcinomas were also stained with GPC3. Although most (7/12, 58.5%) acinar cell carcinomas were GPC3 positive, pancreatic ADCA and neuroendocrine neoplasms were GPC3 negative. In addition, 27.5%, (8/29) of squamous cell carcinomas, 20% (6/30) of ADCA, and 2.5% (1/39) of neuroendocrine carcinomas of the GI tract were immunoreactive for GPC3. HCC was positive for GPC3 in 75% (24/32) of cases but cholangiocarcinoma was negative. While significant correlation between GPC3 positivity and poor differentiation was observed in HCC only, GPC3 expression did not correlate with tumor size. In conclusion, 14% of GI tract and pancreatic carcinomas/neoplasms (particularly pancreatic acinar cell carcinoma) can express GPC3 by immunohistochemistry. As these tumors commonly metastasize to the liver, this offers a potential pitfall in differentiating between HCC and metastatic carcinoma when evaluating tumors involving the liver.
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