Objective: The aim of this study was to evaluate the correlation of protein expressions of CXC chemokine receptor 4 (CXCR4), vascular endothelial growth factor-C (VEGF-C) and cytokeratin 19 (CK-19) with lymph node metastasis (LNM) in patients with hepatocellular carcinoma (HCC), and their survival.
Methods: The expressions of CXCR4, VEGF-C and CK-19 in HCC patients with (n = 123) or without (n = 145) LNM were determined using tissue microarray and immunohistochemical staining. The relationship between clinicopathological features and CXCR4, VEGF-C and CK-19 were analyzed. Evaluation of immunostaining was performed semiquantitatively by visual assessment.
Results: The UICC T stage, and expressions of nuclear CXCR4, VEGF-C and CK-19 were independent risk factors for LNM. Nuclear CXCR4, VEGF-C and CK-19 expression were predictive factors for LNM in HCC patients. In patients with LNM, the median survival time was 15.1 months for patients with high nuclear CXCR4 expression and 24.5 months for those with low nuclear CXCR4 expression. The median survival time was 15.1 months for patients with high tumor VEGF-C expression and 31.1 months for those with low tumor VEGF-C expression. The median survival time was 12.0 months for patients with positive CK-19 expression and 19.2 months for patients with negative CK-19 expression. Patients with high nuclear CXCR4, VEGF-C or CK-19 expression had significantly poorer prognosis than those with low expression (all P < 0.05). PVT, UICC T stage and expressions of nuclear CXCR4, VEGF-C, and CK-19 were independent prognostic factors.
Conclusion: Increased protein expressions of nuclear CXCR4, VEGF-C, and CK-19 are independent risk factors for developing lymph node metastasis, and they are significantly correlated with LNM and poor outcome in HCC patients.