Advantages and Pitfalls of Glypican-3 Immunohistochemistry in the Distinction of Hepatocellular Carcinoma and Metastatic Carcinomas
R Ramachandran, LW Browne, S Kakar. UCSF, San Francisco, CA
Background: Immunohistochemistry for glypican-3 (GPC), a membrane-anchored proteoglycan, has been advocated for the diagnosis of hepatocellular carcinoma (HCC). However, the experience with this antibody is still limited and its expression in adenocarcinomas of various sites and other metastatic tumors that can mimic HCC has not been widely studied.
Design: GPC immunohistochemistry (IHC) was performed on tissue microarrays generated from hepatocellular carcinoma (n=162), adenocarcinomas (n=139) including cholangiocarcinoma and metastatic adenocarcinomas from colon, pancreas, breast and lung. Polygonal cell tumors that can often be mistaken for HCC were also studied including renal cell carcinoma (RCC,n=139), neuroendocrine tumors (NE,n=14), melanoma (n=52) adrenocortical carcinoma (ACC,n=25) and angiomyolipoma (AML,n=57). IHC for polyclonal carcinoembryonic antigen (pCEA), hepatocyte paraffin 1(HepPar) and monoclonal epithelial glycoprotein (MOC-31) was also done.
Marker expression in tissue microarrays*expression in a non-canalicular pattern
|GPC-3 (%)||HepPar (%)||MOC-31 (%)||pCEA (%)|
|HCC||104/162 (64)||100/147 (68)||13/146 (9)||72/163 (44)|
|Adenocarcinoma||3/139 (2)||1/140 (0)||128/143 (90)||122/139 (88*)|
|Melanoma||2/51 (4)||0/58||3/52 (6)||8/58 (14)|
GPC, HepPar and canalicular pCEA were expressed in 64%, 68% and 44% of HCC respectively. All 3 markers were expressed in 26% of HCC. GPC alone was seen in 12%, HepPar alone in 15% and pCEA alone in 1 case (<1%). Rare melanomas (4%) and adenocarcinomas (2%) showed GPC expression. All other adenocarcinomas and polygonal cell tumors were negative. MOC31 was expressed in majority of adenocarcinomas, NE and RCC, but also in 13 (9%) HCC. GPC expression was seen in 9/13 MOC31+ HCC; of these GPC was the only positive heptocellular marker in 6 cases.
Conclusions: GPC has high specificity for HCC with negative or rare expression in metastatic adenocarcinomas, RCC, NE, ACC and AML. The reported GPC expression in melanomas has ranged from 0-80%, and was observed in 4% in this series. MOC31, an excellent adenocarcinoma marker can be strongly expressed in 9% of HCC. GPC is the only hepatocellular marker expressed in 12% of HCC and when combined with HepPar, it increases the sensitivity of HCC diagnosis to >90% and identifies all HCC cases with MOC31+ expression.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 173, Tuesday Morning