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

Histopathology. 2014 Dec;65(6):784-92. doi: 10.1111/his.12497. Epub 2014 Aug 5.


Aims: Our recent proteomic study identified tubulin β-III (TUBB3) as a potential tissue marker for intrahepatic cholangiocarcinomas (CCs). This validation study was conducted to see whether or not TUBB3 can serve as a novel immunohistochemical marker for peripheral CCs, using a large cohort (n = 197) covering various liver tumours and premalignant conditions.

Methods and results: Immunostaining using a monoclonal antibody demonstrated TUBB3 expression in 14/28 cases of peripheral CCs (50%), while its expression was significantly less common in perihilar CCs (6/40, 15%) (P = 0.002). No significant difference was identified in clinicopathological features between TUBB3-positive and -negative cases. TUBB3 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. TUBB3 expression was only focally noted in 2/12 cases of mixed hepatocellular and cholangiocarcinomas (<10% of cancer cells). Compared with other biliary (CK7 and CK19) and malignant markers (p53 and MUC1), TUBB3 was less sensitive but more specific for peripheral CCs. TUBB3 was also expressed in 40% of metastatic colorectal or breast cancers.

Conclusions: This study revealed that TUBB3 is a moderately sensitive and highly specific tissue marker for discriminating peripheral CCs from other primary liver tumours.

Keywords: bile duct; biomarker; cancer; cholangiocarcinoma; liver; proteomics.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology*
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology*
  • Biomarkers, Tumor / analysis*
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Tubulin / analysis
  • Tubulin / biosynthesis*


  • Biomarkers, Tumor
  • TUBB3 protein, human
  • Tubulin