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 1||GPC3||pCEA(canalicular)||MOC-31||CK7||CK19|
|p-value (sHCC vs cHCC)||<0.001||0.02||0.31||<0.001||<0.001||<0.001|