Tubulin β‐ III : a novel immunohistochemical marker for intrahepatic peripheral cholangiocarcinoma

Aims Our recent proteomic study identified tubulin β‐ III ( TUBB 3) as a potential tissue marker for intrahepatic cholangiocarcinomas ( CC s). This validation study was conducted to see whether or not TUBB 3 can serve as a novel immunohistochemical marker for peripheral CC s, using a large cohort ( n  = 197) covering various liver tumours and premalignant conditions. Methods and results Immunostaining using a monoclonal antibody demonstrated TUBB 3 expression in 14/28 cases of peripheral CC s (50%), while its expression was significantly less common in perihilar CC s (6/40, 15%) ( P  = 0.002). No significant difference was identified in clinicopathological features between TUBB 3‐positive and ‐negative cases. TUBB 3 expression was entirely negative in hepatocellular carcinomas, biliary premalignant lesions (i.e., biliary intraepithelial neoplasias, intraductal papillary neoplasms), peribiliary gland hamartomas (bile duct adenomas), and non‐neoplastic biliary epithelium. TUBB 3 expression was only focally noted in 2/12 cases of mixed hepatocellular and cholangiocarcinomas (<10% of cancer cells). Compared with other biliary ( CK 7 and CK 19) and malignant markers (p53 and MUC 1), TUBB 3 was less sensitive but more specific for peripheral CC s. TUBB 3 was also expressed in 40% of metastatic colorectal or breast cancers. Conclusions This study revealed that TUBB 3 is a moderately sensitive and highly specific tissue marker for discriminating peripheral CC s from other primary liver tumours.