卵巢浆液性囊腺癌组织缺氧诱导因子1α的表达及其与临床病理学相关性的研究

Clinicopathologic significance of hypoxia-inducible factor-1α overexpression in ovarian serous cystadenocarcinoma

目的:探讨缺氧诱导因子-1α(hy-poxia-inducible factor-1α,HIF-1α)与卵巢浆液性癌的临床病理参数、肿瘤血管生成及预后评价的关系。方法:用免疫组织化学方法检测HIF-1α、血管内皮生长因子(vascularendothelial growthfactor,VEGF)、碱性成纤维细胞生长因子(basic fibroblast growthfac-tor,bFGF)和CD34蛋白在52例人卵巢浆液性癌组织中的表达,分析HIF-1α与VEGF、bFGF、微血管密度(microvessel den-sity,MVD)及临床病理参数的关系。结果:HIF-1α蛋白在卵巢浆液性囊腺癌和卵巢交界性浆液性囊腺瘤组织中的高表达率明显高于正常卵巢和卵巢浆液性囊腺瘤组织,P分别为0.0005和0.0008;低分化、Ⅲ+Ⅳ期和腹水阳性患者HIF-1α蛋白的高表达率明显高于高中分化、Ⅰ+Ⅱ期和腹水阴性者,P分别为0.033、0.006和0.003;HIF-1α蛋白表达与年龄无关(P=0.437),与VEGF、bF-GF及MVD具有明显的正相关,P分别为0.0001、0.0003和0.0007。结论:HIF-1α与卵巢浆液性囊腺癌血管生成密切相关,在卵巢浆液性囊腺癌的发生发展中起重要作用。

OBJECTIVE： To evaluate the re1αtionship of hypoxia-inducible factor-1α （HIF-1α） expression and clinicopathological features,tumor angiogenesis ,and its value in the prediction of aggressive behavior of ovarian serous cystadenocarcinoma. METHODS ： HIF-1α, vascular endothelial growth factor （VEGF）, and basic fibroblast growth factor （bFGF） expression patterns were examined by immunohistochemistry in 52 specimens. CD34 antigen levels were also examined by immunohistochemistry to determine microvessel density （MVD） within tumors and correlations between HIF-1α expression, and clinicopathological features were examined. RESULTS： HIF-1α expression of normal and serous cystadenomas was significantly lower than that in borderline ovarian serous tumors and carcinomas （P = 0. 000 5, P= 0. 000 8）. HIF-1α expression was significantly stronger in high grade or stages m and Ⅳ or presence of ascites invasive ovarian cancer when compared with low grade or stages Ⅲ and Ⅳ or absence of ascites tumors （P = 0. 033, P = 0. 006, P = 0. 003）. There were no significant differences in HIF-1α expression based on age （P=0. 437）. There was significant correlation of HIF-1α expression with expression of VEGF, bFGF and CD34 in invasive cancers （P=0. 000 1,P=0. 000 3,P=0. 000 7）. CONCLUSION.. It is suggested that HIF-1α may play an important role in aggressive behavior and tumor angiogenesis in ovarian serous cystadenocarcinoma.