FAT, E-cadherin, beta catenin, HER 2/neu, Ki67 immuno-expression, and histological grade in intrahepatic cholangiocarcinoma.

Objective: To identify surrogate prognostic markers in intrahepatic cholangiocarcinoma (IHCC).

Methods: Thirty one cases of IHCC were graded and immunostained for FAT, Ki67, E-cadherin, beta catenin, and HER 2/neu.

Results: Twenty two cases were high grade and 27 had high Ki67 counts. Strong membranous staining of HER 2/neu was found in 10 tumours and reduced membranous E-cadherin and beta catenin in 19 and 18 tumours, respectively. Nuclear localisation of beta catenin was identified in five tumours and 22 showed weak cytoplasmic staining of FAT. Strong HER 2/neu and weak FAT immuno-expression were significantly correlated with high histological grade (p=0.01) and high Ki67 index (p=0.03). Upregulation of HER 2/neu was also significantly associated with nuclear localisation of beta catenin (p=0.01). Reduced membranous beta catenin was significantly related to reduced membranous E-cadherin (p=0.03), weak staining for FAT (p=0.01), and nuclear translocation of beta catenin (p=0.04).

Conclusions: Reduced immuno-expression of E-cadherin and FAT at their normal membranous location may be potential prognostic markers, and the overexpression of HER 2/neu and beta catenin nuclear translocation may have a role in cholangiocarcinogenesis.