HIF-1α、2α和Survivin蛋白在结肠腺癌中的表达及临床意义

EXPRESSION OF HIF-1α、HIF-2α AND SURVIVIN IN COLON ADENOCARCINOMA AND THEIR CLINICAL SIGNIFICANCES

目的探讨缺氧诱导因子(HIF-1α、HIF-2α)和生存素蛋白(Survivin)在结肠正常粘膜、结肠腺瘤、结肠腺癌组织中的表达,初步分析缺氧诱导因子、生存素蛋白与结肠腺癌生物学行为之间的关系。方法采用免疫组织化学(SP)方法,分别检测结肠正常粘膜、结肠腺瘤和结肠腺癌组织中HIF-1α、HIF-2α和Survivin的表达。结果(1)HIF-1α、HIF-2α和Survivin在结肠正常粘膜组织中不表达,在结肠腺瘤组织中低表达,在结肠腺癌中高表达;结肠不同组织分型中三者表达比较有显著性差异(P<0.01),随正常粘膜—腺瘤—癌的次序三者表达呈逐渐升高趋势。(2)HIF-1α、HIF-2α和Survivin在结肠腺癌组织中表达越强,淋巴结转移率越高(P<0.01)、组织分化程度越低(P<0.05)、Dukes分期越晚(P<0.05)。(3)结肠腺癌中HIF-1α、HIF-2α表达与Survivin表达呈正相关(P<0.01)。结论(1)HIF-1α、HIF-2α和Survivin过度表达对结肠腺癌的发生、发展起正性协同作用,三者与结肠腺癌的浸润、转移密切相关。(2)检测结肠腺癌组织中Survivin的表达对判断肿瘤的发生、进展具有重要意义。Survivin可望成为诊断和治疗结肠腺癌的新靶点。

Objective To investigate the expression of hypoxia - inducible factor （ HIF - 1α, HIF - 2α） and survivin protein （survivin） expression in the normal colon mucosa, colorectal adenomas and colon cancer tissues. Preliminary analysis was carried out to determine the relationship hypoxia - inducible factor and survivin protein between colon adenocarcinoma concerned biological behavior. Methods Immunohistochemistry （SP） methods were used to detect HIF- 1α, HIF- 2α and survivin expression in colon normal mucosa, colorectal adenomas and colon adenocarcinoma tissue. Results （1） HIF-1α, HIF- 2α and were not expressed in normal colonic mucosal tissues;but showed low expression in colon adenoma tissue and high expression in colon adenocarcinoma. The three factors expression in different colon tissue types showed with the trend of ordered in normal mucosa -adenoma significant difference （P 〈 0.01 ）. The expression increased - cancer. （2） the stronger HIF - 1 α, HIF - 2α and survivin in colon adenocarcinoma tissues expression, the higher rate of lymph node metastasis （ P 〈 0. 01 ） and lower degree of differentiation （ P 〈 0.05 ） or the later Dukes stages were observed （ P 〈 0.05 ）. （3） The expression of HIF - 1α, HIF - 2α and survivin in colon adenocarcinoma was positively correlated （ P 〈 0.01 ）. Conclusion （ 1 ） Over - expression of HIF - 1α, HIF -2α and survivin has the effect of positive synergy for the colon adenocarcinoma onset and development. Three factors are closely related to invasion and metastasis of colon adenocarcinoma. （2） Detection of survivin expression on colon adenocarcinoma showed great importance to determine the occurrence and progress of the tumor. Survivin is expected to become a new target for the diagnosis and treatment of colon adenocarcinoma.