The αvβ6 integrin is a highly specific immunohistochemical marker for cholangiocarcinoma

作者：Eleonora Patsenker, Ludwig Wilkens, Vanessa Banz, C.H. Österreicher, R. Weimann, S. Eisele, Adrian Keogh, Deborah Stroka, A. Zimmermann, Felix Stickel · 发表于：Journal of Hepatology · 年份：2010 · DOI：10.1016/j.jhep.2009.12.006 · 被引用次数：58 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Liver Diseases and Immunity、Liver physiology and pathology

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 alphavbeta6 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 alphavbeta6 integrin in differentiating primary liver cancers. METHODS: Expression of alphavbeta6 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 beta6 subunit was compared with CK7, CK20, and HepPar 1. RESULTS: In CC cells beta6 mRNA levels were induced 125-fold compared to primary cholangiocytes, while it was completely absent in hepatoma cells. In human tissues, beta6 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 alphavbeta6, whereas all HCC, combined CC/HCC and fibrolamellar HCC stained negative. Specificity of beta6 immunohistochemistry for CC (100%) surpassed all other tested markers and sensi...