Clinical significance of cytokeratin 19 expression in hepatocellular carcinoma

Aim: This study aimed to compare the prognostic outcomes of cytokeratin (CK) 19-positive and CK19-negative hepatocellular carcinoma (HCC), focusing on clinicopathological features and the impact of targeted therapy in CK19-positive patients. Methods: A retrospective analysis was performed on 310 HCC patients who underwent curative resection between 2010 and 2020 at the First Affiliated Hospital of Nanjing Medical University. Among them, 168 were CK19-positive and 102 were CK19-negative. Multivariate Cox regression was used to identify independent predictors of overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier survival curves were generated from the Cox model. Results: CK19-positive patients exhibited significantly poorer tumor differentiation (P < 0.001), increased microvascular invasion (P = 0.010), elevated α-fetoprotein (AFP) (P = 0.0001) and were more often asymptomatic at diagnosis (P = 0.014). The median survival time (MST) was 22.1 months in CK19-positive versus 60.3 months in CK19-negative patients. Among those with recurrence, MST was 56.4 months for CK19-positive and 101.6 months for CK19-negative patients. CK19 status significantly impacted OS (P < 0.001) and RFS (P = 0.006) in advanced-stage cases. Independent prognostic factors for RFS included cirrhosis, tumor size, number of tumors, macrovascular invasion, poor differentiation, and CK19 expression. Microvascular invasion and Child-Pugh classification were additional predictors of OS. Targeted therapies did not significantly improve outcomes in CK19-positive patients. Conclusions: CK19-positive HCC is associated with more aggressive tumor behavior, higher recurrence, and poorer survival. Targeted therapy provided no significant survival benefit in this study.