缺氧诱导因子1α的表达与卵巢浆液性囊腺癌血管生长相关性的研究

Relationship of Hypoxia-inducible Factor-1α Overexpression and Tumor Angiogenesis in Ovarian Serous Cystadenocarcinoma

目的探讨缺氧诱导因子1α(HIF-1α)与肿瘤血管生成的关系以及HIF-1α在卵巢浆液性癌发生和发展中的作用。方法免疫组织化学方法检测HIF-1α、VEGF、bFGF、PCNA、CD34蛋白在52例人卵巢浆液性癌组织中的表达,标记肿瘤内微血管密度(MVD),分析HIF-1α与VEGF、bFGF、PCNA、MVD及临床病理参数的关系。结果HIF-1α、VEGF、bFGF蛋白在卵巢浆液性囊腺癌和卵巢交界性浆液性囊腺瘤中的高表达率明显高于正常卵巢组织和卵巢浆液性囊腺瘤,其差异有显著性(P<0.01);低分化、Ⅲ期+Ⅳ期和腹水阳性HIF-1α蛋白的高表达率明显高于高中分化、Ⅰ期+Ⅱ期和腹水阴性者,差异具有显著性(P<0.05);HIF-1α蛋白表达与年龄无关(P>0.05);HIF-1α蛋白表达与VEGF、bFGF、PCNA及MVD具有明显的正相关(P<0.01);Cox模型分析,VEGF及MVD是晚期卵巢浆液性囊腺癌的独立预后因素(P<0.05)。结论HIF-1α与卵巢癌血管生成密切相关,在卵巢癌的发生、发展中起着重要作用。

Objective The objective of this study was to evaluate the relationship of hypoxia-inducible factor-1α（HIF-1α） expression and clinicopathological features,tmnor angiogenesis,recurrence/distant metastasis , and its value in the prediction of aggressive behavior of ovarian serous cystadenocarcinoma. Methods We examined HIF-1α,vascular endothelial growth factor （VEGF）,basic fibroblast growth factor （bFGF）, and proliferating cell nuclear antigen（PCNA） expression patterns immunohistochemically in 52 specimens.CD34 antigen levels were also examined by immunohistochemistry to determine microvessel density （MVD） within tmnors and correlations between HIF-1α expression, clinicopathological features, and recurrence/distant metastasis were examined, the data were analyzed with X^2 test or Fisher＇s exact test and multivariate test. Results HIF-1α,VEGF,bFGF,PCNA expression of normal and cystadenomas was significantly lower than in LMP tmnors and carcinomas （P 〈 0.01 ）.There was significant correlation of H/F-let expression with expression of VEGF, bFGF, CD34, PCNA in invasive cancers ,LMP tmnors ,and cystadenomas （P 〈 0.01 ）. H/F-let expression was significantly stronger in lower grade or stages Ⅲand Ⅳor presence of ascites invasive ovarian cancer when compared with high grade or stages Ⅰ andⅡ or absence of ascites tumors （P 〈 0.05 ）.There were no significant differences in H/F-let expression based on age （P 〉 0.05）.In addition,the incidence of recurrence/distant metastasis was significantly higher in cases of high HIF-1α,VEGF,bFGF,CD34,PCNA expression than in cases of low expression（P 〈 0.05 ）. expression of VEGF and MVD are two independent prognostic factors in ovarian serous cystadenocarcinoma（P 〈 0.05）. Conclusion Our findings suggest that H/F-1α may play an important role in aggressive behavior and tmnor angiogenesis in ovarian serous cystadenocarcinoma.In addition,high expression of H/F-1α was significantly correlated with tmnor recurrence/distant metastasis.