Institute of Clinical Pharmacology and Visceral Research, University of Bern, Murtenstrasse 35, Bern, Switzerland.
J Hepatol. 2010 Mar;52(3):362-9. doi: 10.1016/j.jhep.2009.12.006. Epub 2010 Jan 13.
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.
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.
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 sensitivity was equal to CK7 (86% vs. 90%).
The alphavbeta6 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.
肝细胞癌（HCC）和胆管细胞癌（CC）是常见的原发性肝恶性肿瘤。使用特定标志物对其进行免疫组织化学鉴别对于治疗和预后至关重要。我们发现αvβ6 整联蛋白在胆管纤维化中强烈上调，但它在原发性和继发性肝肿瘤中的表达尚不清楚。在此，我们旨在评估αvβ6 整联蛋白在鉴别原发性肝癌中的诊断适用性。
通过免疫组织化学和细胞化学以及 TaqMan PCR 评估 CC、HCC、纤维板层 HCC、CC/HCC 混合癌、结直肠癌和胰腺癌肝转移、原发性硬化性胆管炎（PSC）患者的肝组织以及人原发性和肿瘤衍生的肝细胞系中 αvβ6 整联蛋白的表达。将β6 亚基的诊断性能与 CK7、CK20 和 HepPar 1 进行比较。
在 CC 细胞中，β6 mRNA 水平与原代胆管细胞相比诱导了 125 倍，而在肝癌细胞中完全不存在。在人类组织中，β6 转录物在 CC 中比正常肝脏高 100 多倍。通过免疫组织化学，88%的 CC、50%的 PSC、13%的结直肠癌转移和 80%的胰腺癌转移呈 αvβ6 阳性，而所有 HCC、CC/HCC 混合癌和纤维板层 HCC 均呈阴性。β6 免疫组化对 CC 的特异性（100%）超过了所有其他测试的标志物，其敏感性与 CK7 相同（86%对 90%）。
αvβ6 整联蛋白在人 CC 中强烈表达，但在 HCC 中不表达，因此可被视为原发性肝肿瘤鉴别诊断中的特异性免疫组织化学标志物。
