口腔鳞状细胞癌组织中HIF-1α,VEGF-C的表达及与淋巴管生成的关系

HIF-1α Expression Correlates with VEGF-C Expression and Lymphangiogenesis in OSCC

目的:研究口腔鳞状细胞癌(Oral squamous cell carcinoma,OSCC)组织中乏氧诱导因子-1α(Hypoxiainducible factor-1α,HIF-1α),血管内皮生长因子-C(vascular endothelial growth factor,VEGF-C)表达水平及微淋巴管密度(LVD),探讨其临床病理意义及在口腔鳞状细胞癌中的相互关系。方法:应用免疫组织化学SP法检测65例口腔鳞状细胞癌中HIF-1α,VEGF-C,淋巴管内皮细胞透明质酸受体-1(Lymphatic vessel endothelial hyaluronic acid receptor-1,LYVE-1)的表达并计数LVD。结果:65例OSCC中有43例HIF-1α呈(66.2﹪)高表达,VEGF-C有34例(52.3﹪)高表达。HIF-1α和VEGF-C高表达的病例中都出现高淋巴管密度。HIF-1α高表达分别与VEGF-C高表达显著相关(P<0.05,χ2检验),与高淋巴管密度显著相关(P<0.01,Mann–Whitney U-test),与区域淋巴结转移显著相关(P<0.01,χ2检验)而且也同UICC TNM分期相关(P<0.05,χ2检验)。结论:OSCC中HIF-1α可能通过上调VEGF-C的表达来诱导淋巴管生成并最终导致肿瘤细胞发生区域淋巴结转移。

Objective： To investigate hypoxia--inducible factor--1α（HIF--1α） protein expression, vascular endo- thelial growth factor--C （VEGF--C） protein expression, and lymphatic vessel density（LVD）in oral squamous cell carcinoma （OSCC） and to evaluate, the association between the HIF--1α expression and the clinicopathological parameters was evaluated. Methods： HIF--1α and VEGF--C protein expression were investigated by means of immunohistochemistry in samples from 65 cases of OSCC. The density of the lymphatic microvessels immunohistochemically stained by LYVE--1 antibody, respectively, was calculated. Results： HIF--1α overexpression occurred in 43 out of the 65 tumor samples （66.2%）, while VEGF--C overexpression was observed in 34 out of the 65 tumor samples （52.3%）. Higher LVD was found in both high HIF--1α and high VEGF--C expression cases. HIF--1α overexpression was significantly correlated with VEGF--C overexpression （P〈0. 05, Chi--square test）, higher LVD （P〈0.01, Mann - Whitney U--test）, and regional lymph nodal involvement （P〈0.01, Chi--square test） as well as UICC TNM classification （P〈0.05, Chi--square test）, respectively. Conclusion： HIF--1α overexpression may induce lymphangiogenesis and regional lymph node metastasis through mediating VEGF--C upregulation in human OSCC.