Role of immunophenotypic characterisation in prognostic subtyping of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is classified by the 5th WHO classification of tumours of the digestive system as large duct type (LDT) and small duct type (SDT), based on the anatomical location, morphological appearances, immunophenotype, and gene events. We evaluated the subtyping system using real-world data and established a supplementary method using immunohistochemical (IHC) detection. We retrospectively investigated 190 cases of surgically resected iCCA and classified them according to histological evaluations and gene detection. The prognostic value of the IHC markers were evaluated according to the relapse-free survival (RFS) and overall survival (OS). Basic histological classification was insufficient, with 61 cases classified as uncertain. This method showed no prognostic value for RFS or OS. The four-marker IHC detection, including EMA, S100P, N-cadherin, and CRP, which classified 68 cases as LDT, 108 cases as SDT, and 14 cases as uncertain, was highly efficient in subtyping and prognosis. The seven-marker method, including CD56, MUC5AC and MUC6, was consistent with the four-marker method. FGFR2 gene fusion was exclusively detected in 20 cases of SDT iCCA, according to the four- and seven-marker IHC detection. This novel method of iCCA classification exhibited diagnostic, prognostic and therapeutic value in clinical practice.