The prognostic impact of differentiation at the invasive front of biliary tract cancer

Background The invasive front of tumor can provide prognostic information in many cancers. We investigated the prognostic morphological factors at the invasive front including tumor differentiation (Difinv) and tumor budding (Bud) in biliary tract cancer (BTC). Methods The resected specimen from the 299 BTC patients were examined. Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer were found in 16%, 48%, 17%, and 19%, respectively. Difinvgrade (G) 3 and Bud foci ≥5 were found in 47% and 10%. Tumor with DifinvG3 showed the high frequencies of Bud, vascular invasion (Ve) and nodal metastasis (LN) compared to tumor with DifinvG1/2 (Bud: 21% vs 0%, Ve: 71% vs 50%, LN: 52% vs 36%). Multivariate analysis revealed that the independent predictors were DifinvG3 (HR: 1.71), Bud foci ≥5 (HR: 2.14), Ve (HR: 1.56) and LN (HR: 2.59) in overall survival and were positive resection margin (HR: 1.71), DifinvG3 (HR: 1.75), Ve (HR: 1.50), and LN (HR: 2.19) in relapse free survival. Conclusion Poor differentiation at the invasive front of tumor was associated with poor prognosis and early relapse in BTC patients.