Glypican-3 Expression in Gastrointestinal and Pancreatic Carcinomas
Taofic Mounajjed, Lizhi Zhang, Tsung-Teh Wu. Mayo Clinic, Rochester, MN
Background: Glypican-3 (GPC3), a cell membrane bound proteoglycan that can be overexpressed in certain malignancies, has been particularly linked to hepatocellular carcinoma (HCC). GPC3 is currently used as an immunohistochemical (IHC) marker of HCC but its expression in carcinomas of the gastrointestinal (GI) tract and pancreas, a common source of liver metastasis, has not been studied in detail. This study aims to evaluate GPC3 expression in carcinomas of the GI tract and pancreas.
Design: We examined IHC expression of GPC3 in 158 carcinomas including 52 adenocarcinomas (ADCA) of the pancreas and GI tract (8 esophagus, 8 stomach, 2 small bowel, 12 colon), 29 squamous cell carcinomas (SCC) of the GI tract (19 esophagus and 10 anus), 65 neuroendocrine carcinomas (NECA) of the pancreas and GI tract (2 esophagus, 8 stomach, 15 small bowel, 14 colon), and 12 pancreatic acinar cell carcinomas. Two control groups (32 HCC and 16 intrahepatic cholangiocarcinomas) were also stained with GPC3. All tumors were scored for cytoplasmic and membranous staining. A tumor was considered positive for GPC3 if >10% of neoplastic cells showed strong cytoplasmic and membranous immunoreactivity.
Results: 22 of 158 extrahepatic tumors (14%) were positive for GPC3. In the hepatic tumor group, none (0/16) of the cholangiocarcinomas and 24/32 (75%) of HCC were GPC3 positive. In extrahepatic tumors, GPC3 immunoreactivity was most frequent in pancreatic acinar cell carcinomas (58.5%), followed by SCC (27.5%), and ADCA of theGI tract (20%). All pancreatic ADCAs and NECAs were GPC3 negative. GPC3 expression correlated with poor differentiation in HCC but no such correlation was present in extrahepatic tumors. GPC3 positivity was more frequent in upper GI tract ADCA (28%) compared to lower GI tract ADCA (8.5%). In all tumors including HCC, GPC3 expression showed no significant correlation with tumor size. In all positive tumors, GPC3 immunoreactivity was characterized by strong cytoplasmic and membranous staining of 20-100% of the neoplastic cells. Diffuse positivity occupying 100% of tumor cells was only observed in HCC and pancreatic acinar cell carcinoma. SCCs typically demonstrated a predominant peripheral/basal distribution of GPC3 immunoreactivity.
Conclusions: GPC3 immunoreactivity occurs frequently in carcinomas of the GI tract and pancreas and is most often observed in pancreatic acinar cell carcinoma, SCC, and ADCA of the upper GI tract. As these tumors commonly metastasize to the liver, this can lead to a mistaken diagnosis of HCC; GPC3's lack of specificity should be recognized when evaluating tumors involving the liver to avoid potential diagnostic pitfalls.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 139, Tuesday Morning