食管癌组织VEGF-C SDF-1/CXCR4的表达及其与淋巴结转移关系的研究

Expression of VEGF-C, SDF-1, and CXCR4 in esophageal carcinoma and its relationship with lymph node metastasis

目的:研究VEGF-C、SDF-1及CXCR4在食管鳞癌中的表达,并分析其与食管癌相关临床病理因素的关系和对预后的影响。方法:通过免疫组织化学SP法检测VEGF-C、SDF-1及CXCR4在95例食管癌切除组织中的表达,并探讨其临床意义。结果:VEGF-C及SDF-1、CXCR4三种因子蛋白表达均主要位于肿瘤细胞的胞质,阳性率分别为89.5%、84.2%、69.5%,其中CXCR4在肿瘤细胞中未见到强阳性表达。VEGF-C和SDF-1在肿瘤细胞的表达与肿瘤细胞分化程度、浸润深度、淋巴结转移和转移的个数以及病理TNM分期均有相关性,其中有淋巴结转移组的VEGF-C和SDF-1表达率均高于无淋巴结转移组,且差异均有统计学意义(χ2=6.319,P=0.012;χ2=5.821,P=0.016)。而CXCR4在肿瘤细胞的表达仅与肿瘤细胞分化程度相关,且分化越高表达越强。多因素分析显示淋巴结转移、淋巴结转移数目、病理TNM分期及SDF-1蛋白表达为影响预后的独立性因素(P<0.05)。结论:食管鳞癌组织中VEGF-C、SDF-1的表达与多项临床病理指标尤其是淋巴结转移程度有关,其中SDF-1可作为淋巴结转移及预后的免疫病理学指标,同时VEGF-C与SDF-1/CXCR4在淋巴结转移中可能有协同作用。

Objective： This work aims to investigate the expressions of vascular endothelial growth factor-c （VEGF-C）, stromal cell- derived factor-1 （SDF-1）, and human chemokine （C-X-C motif） receptor 4 （CXCR4） in esophageal squamous cell carcinoma. In addition, their correlation with clinicopathological factors and their effect on the prognostic value are also investigated. Methods： The immunohistochemical expressions of VEGF-C, SDF-1, and CXCR4, the relationship among them, and the clinicopathological factors including nodal metastasis and prognostic value in the surgical specimens from 95 patients with primary esophageal squamous cell car- cinoma were assayed. Results： VEGF-C, SDF-1, and CXCR4 proteins were mainly located in the cytoplasm of the tumor cells. The positive expression rates of VEGF-C, SDF-1, and CXCR4 were 89.5%, 84.2%, and 69.5%, respectively. The positive expressions of VEGF-C and SDF-1 were significantly correlated with the cellular differentiation degree, tumor invasion depth, nodal metastasis, num- ber of nodal metastasis, and the tumor, node, and metastasis （TNM） stage as defined by the World Health Organization. The positive rates of VEGF-C and SDF-1 expressions were higher in patients with lymph node metastasis than in those without lymph node. Signifi- cant differences were observed between the two （χ2=6.319, P=0.012; χ2=5.821, P=0.016）. However, the positive expression of the CX- CR4 protein was only correlated with the cellular differentiation degree. The Kaplan-Meier survival analysis results show the tumor in- vasion depth, lymph node metastasis, number of the metastasized lymph nodes, pathological TNM （pTNM） stage, and the expressions of VEGF-C, SDF-1, and CXCR4. The multivariate analysis results show that the tumor invasion depth, nodal metastasis, number of metastatic lymph nodes, pTNM stage, and expression of SDF-1 were independent prognostic factors. Conclusion： The expressions of VEGF-C and SDF-1 proteins exhibit a correlation with the clinicopathological variables, especially the lymph node metastasis. Evaluat- ing the SDF-1 expression is useful to determine tumor characteristics, such as nodal metastasis and prognosis, in patients with esopha- geal squamous cell carcinoma. Moreover, VEGF-C and SDF-1/CXCR4 proteins may have a synergistic effect on the lymph node metas- tasis of esophageal squamous cell carcinoma.