The αvβ6 integrin is a highly specific immunohistochemical marker for cholangiocarcinoma

Background & Aims: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are common primary hepatic malignancies. Their immunohistological differentiation using specific markers is pivotal for treatment and prognosis. We found alpha v beta 6 integrin strongly upregulated in biliary fibrosis, but its expression in primary and secondary liver tumours is unknown. Here, we aimed to evaluate the diagnostic applicability of alpha v beta 6 integrin in differentiating primary liver cancers. Methods: Expression of alpha v beta 6 integrin was evaluated in liver tissues from patients with CC, HCC, fibrolamellar HCC, combined CC/HCC, hepatic metastases of colorectal and pancreatic carcinomas, primary sclerosing cholangitis (PSC), and in human primary and tumour-derived liver cell lines by immunohisto- and cytochemistry, and by TaqMan PCR. Diagnostic performance of the 136 subunit was compared with CK7, CK20, and HepPar 1. Results: In CC cells beta 6 mRNA levels were induced 125-fold compared to primary cholangiocytes, while it was completely absent in hepatoma cells. In human tissues, beta 6 transcripts were more than 100-fold upregulated in CC compared to normal liver. By immunohistochemistry, 88% of CC, 50% of PSC, 13% of colorectal carcinoma metastases, and 80% of pancreatic carcinoma metastases presented alpha v beta 6, whereas all HCC, combined CC/HCC and fibrolamellar HCC stained negative. Specificity of beta 6 immunohistochemistry for CC (100%) surpassed all other tested markers and sensitivity was equal to CK7 (86% vs. 90%). Conclusion: The alpha v beta 6 integrin is strongly expressed in human CC but not in HCC and therefore can be considered as a specific immunohistochemical marker in the differential diagnosis of primary liver tumours. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.