Expression of p16INK4a and its clinicopathological and survival outcomes in cholangiocarcinoma: A retrospective cohort study

Cholangiocarcinoma (CCA) is an aggressive adenocarcinoma arising from the epithelium of intrahepatic and extrahepatic bile ducts with distinct growth patterns. CCA is associated with poor clinical outcomes. The CDKN2A and one of its protein products, p16INK4a, which is frequently downregulated in CCA, may contribute to disease pathogenesis. To evaluate the prognostic significance of p16INK4a expression using immunohistochemistry in CCA patients and analyze its correlation with clinicopathological parameters. A retrospective cohort study analyzing 180 CCA patients diagnosed at Srinagarind Hospital, Khon Kaen, Thailand, between 2017 and 2023. Positive/high p16INK4a expression was detected in 61 cases (33.9 %) and showed association with mixed tumor growth patterns (p = 0.041). While p16INK4a expression did not significantly impact overall survival in Kaplan–Meier analysis (p = 0.745), the patients with positive/high expression showed a trend toward shorter median survival time compared to that of the negative/low expression group (13 vs. 18 months, p = 0.015). p16INK4a expression is not independently associated with survival, however high expression is associated with histologically mixed growth patterns and might influence tumor differentiation in CCA. These results suggest p16INK4a may contribute to CCA progression, particularly in complex growth patterns and poor differentiation. Further study is warranted to fully elucidate its clinical significance and potential therapeutic implications.