Evidence-Based Immunohistochemical Panel for the Distinction of Hepatocellular Carcinoma and Metastatic Carcinoma
R Ramachandran, LW Browne, I Mehdi, Y Chen, S Kakar. UCSF, San Francisco; Kaiser, Walnut Creek
Background: Commonly used markers for diagnosis of hepatocellular carcinoma(HCC) have several limitations. The sensitivity of Hepatocyte Paraffin 1(HepPar) and polyclonal CEA(pCEA) is ∼80%, but is low in poorly differentiated cases. Glypican-3(GPC) helps in identification of poorly differentiated HCC, but its specificity is not well established. Adenocarcinoma(AC) markers like MOC31,CK7 and CK19 can be positive in a subset of HCC. Since limited tissue is available in most cases, it is desirable to determine the combination of markers that will yield the highest sensitivity and specificity.
Design: Immunohistochemistry was performed on tissue microarrays generated from 161 HCC, 23 neuroendocrine tumors(NE) and 386 ACs(65 gastroesophageal,6 pancreaticobiliary,55 lung,205 breast,55 colorectal). Three hepatocellular(HepPar,GPC,pCEA) and 5 AC markers(MOC31,CK7,CK19,BerEP4,B72.3,CD15) were evaluated.
Results: HepPar was the most sensitive hepatocellular marker and along with GPC yielded a sensitivity of >95% for HCC. HepPar and GPC were positive in <5% of AC and NE; their combined expression was not seen in any non-HCC case. MOC31 was the most sensitive marker for NE and AC irrespective of site. Addition of CK7 or CK19 to MOC31 increased the sensitivity to 97% for AC and 100% for NE. CK19 had higher sensitivity than CK7 for AC and NE. The characteristic HepPar+/MOC31- phenotype was seen in 71% of HCC. MOC31 was strongly expressed in 13(10%) HCCs; HepPar was negative in 9 of these cases. In 12 of these, CK19 was negative; GPC was positive in 10 of these cases. The addition of GPC and CK19 correctly identified 12 of 13 cases with aberrant HepPar-/MOC31+ immunophenotype.