[1553] Immunohistochemical Pitfalls and the Importance of Glypican-3 in the Diagnosis of Scirrhous Hepatocellular Carcinoma.

Gregor Krings, Dhanpat Jain, Tsung-Teh Wu, Matthew Yeh, Michael Torbenson, Sanjay Kakar. UCSF, San Francisco, CA; Yale Univ, New Haven, CT; Mayo Clinic, Rochester, MN; Univ of Washington, Seattle; Johns Hopkins, Baltimore, MD

Background: Scirrhous hepatocellular carcinoma(sHCC)is a rare subtype of HCC which can mimic cholangiocarcinoma(CC)or metastatic adenocarcinoma(MA).sHCC tends to be negative for Hep Par 1(Hep)and often expresses CK7,further confounding the diagnostic dilemma.Glypican-3 (GPC) is an oncofetal antigen that has higher sensitivity than Hep for poorly-differentiated conventional HCC(cHCC).Expression of GPC and other markers used in distinction of HCC and adenocarcinoma including polyclonal carcinoembryonic antigen(pCEA),MOC-31 and CK19 have not been systematically evaluated in sHCC.
Design: Immunohistochemistry for Hep,GPC,pCEA,MOC31,CK7 and CK19 was performed on 12 sHCC cases,and scored as 0(negative),1(weak),2(moderate)and 3(strong).The number of positive cells were recorded as focal(<10%),patchy(10-50%)or diffuse(>50%).Score of at least 2+ in >10% of cells was regarded as positive.The results were compared with previously characterized cHCC(n=160)and CC(n=12).
Results: In all sHCC,stroma comprised >50% of tumor.In 2 cases,sHCC was admixed with areas of cHCC.Hep was positive in 2(17%)sHCC;GPC3 and pCEA were positive in 12(100%) and 4(33%)cases respectively.Diffuse staining was seen in 10(83%)cases with GPC,compared to 1(8%)with Hep and none with pCEA.Adenocarcinoma markers, MOC31,CK7 and CK19 were positive in 64%,58% and 36% cases respectively. At least one adenocarcinoma marker was positive in 10(83%)cases and at least two in 5(42%)cases.Of 2 cases with admixed cHCC,staining in cHCC was same as sHCC area in 1 case;the other case showed Hep positivity in cHCC area but not in sHCC portion.Staining results in sHCC were significantly different compared to cHCC.All CC were GPC-negative.

 Hep Par 1GPC3pCEA(canalicular)MOC-31CK7CK19
sHCC(n=12)1710033645836
cHCC(n=160)7570541122
CC (n=12)000100100100
p-value (sHCC vs cHCC)<0.0010.020.31<0.001<0.001<0.001
Figures reflect percentages


Conclusions: In contrast to cHCC,most sHCC are negative for Hep,and frequently express adenocarcinoma markers like MOC31,CK7 and CK19.This aberrant immunophenotype along with presence of prominent stroma can be confused with CC or MA. GPC is expressed in all sHCC with diffuse expression in most cases.Addition of GPC to the immunohistochemical panel can facilitate the diagnosis of sHCC.
Category: Liver & Pancreas

Tuesday, March 1, 2011 9:30 AM

Poster Session III # 254, Tuesday Morning

 

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