趋化因子受体4核阳性以及血管内皮生长因子C和细胞角蛋白19的表达水平与肝细胞癌淋巴结转移风险的关系

Nuclear accumulation of CXCR4 and overexpressions of VEGF-C and CK-19 are associated with a higher risk of lymph node metastasis in hepatocellular carcinoma

目的 探讨趋化因子受体4（CXCR4）、血管内皮生长因子C（VEGF-C）和细胞角蛋白19（CK-19）蛋白在肝细胞癌（HCC）肿瘤组织中的表达,以及与淋巴结转移和患者预后的关系.方法 收集123例术后出现淋巴结转移和145例术后无淋巴结转移的HCC石蜡包埋组织,制备组织芯片;采用免疫组化半定量法检测CXCR4、VEGF-C和CK-19蛋白的表达水平,并分析3种蛋白的表达与HCC淋巴结转移和其他临床病理因素之间的关系.结果 T分期、细胞核CXCR4蛋白的表达、VEGF-C蛋白的表达和CK-19蛋白的表达是HCC发生淋巴结转移的独立因素.细胞核CXCR4蛋白、VEGF-C蛋白高表达和CK-19蛋白阳性能预测HCC的淋巴结转移.123例有淋巴结转移的HCC患者中,细胞核CXCR4蛋白高表达和低表达患者的中位生存时间分别为15.1和24.5个月;VEGF-C蛋白高表达和低表达患者的中位生存时间分别为15.1和31.1个月;CK-19蛋白阳性和阴性患者的中位生存时间分别为12.0和19.2个月.细胞核CXCR4蛋白、VEGF-C蛋白高表达和CK-19蛋白阳性患者的预后均明显差于相应的低表达组和阴性组（均P〈0.05）.有无门脉癌栓、T分期、细胞核CXCR4蛋白和VEGF-C蛋白的表达以及CK-19蛋白的表达是伴淋巴结转移的HCC患者的独立预后因素.结论 细胞核CXCR4蛋白、VEGF-C高表达和CK-19蛋白阳性与HCC淋巴结转移和预后差有关,并可作为HCC淋巴结转移的独立预后因素.

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.