乳腺癌组织中COX-2、HIF-1α表达及其预后意义

The Expression of COX-2 and HIF-1α in Breast Cancer and the Correlation with Clinicopathologic Characteristic and Prognosis

目的:环氧化酶-2(COX-2)是前列腺素合成的限速酶,参与多种恶性肿瘤的发生及发展,但其发病机制并不清楚。近年研究发现:缺氧诱导因子-1α(HIF-1α)参与COX-2的表达,并与肿瘤的预后有关。本文应用免疫组化法,检测COX-2、HIF-1α在乳腺癌组织中表达,探讨COX-2、HIF-1α表达与乳腺癌临床病理特征及预后因素的关系。方法:122例乳腺癌组织石蜡标本制作成乳腺癌组织芯片。免疫组化SP法检测COX-2、HIF-1α表达。所有患者均接受规范性手术、术后辅助化疗及放疗,激素受体阳性病人接受5年的内分泌治疗。从手术日期到复发转移或随访截止日期(2011年7月)确定为患者无病生存期。共有45例复发转移病例。结果:①122例乳腺癌组织中COX-2、HIF-1α均呈高表达,分别为58.2%、51.6%,且二者表达呈正相关(r=0.313,P=0.001);②COX-2表达与临床分期(r=0.193,P=0.033)、肿块大小(r=0.192,P=0.034)及淋巴结转移(r=0.245,P=0.040)呈正相关,HIF-1α表达与临床分期(r=0.209,P=0.037)、肿块大小(r=0.345,P=0.001)、淋巴结转移(r=0.245,P=0.002)呈正相关;③COX-2或HIF-1α表达与无病生存期呈负相关(P值分别=0.027,P=0.034)。结论:乳腺癌组织中COX-2、HIF-1α均呈高表达,两者与乳腺癌患者预后密切相关;COX-2、HIF-1α表达呈正相关,我们推测乳腺癌组织中HIF-1α可能参与COX-2调节。

Objective：High incidence rates of over-expression COX-2 was found in breast cancer patients.Over-expression had been associated with a poor clinical outcome,but the mechanism is not clear.An abroad document indicated HIF-1αup-regulated expression COX-2 in non-small cell lung cancer cells in vitro.Another document reported that over-expression HIF-1αwas correlated with prognosis in colorectal cancer patients.In this study,we detected the expression of COX-2 and HIF-1α using immunohistochemical SP methods to investigate the relationship between them,as well as to correlate with clinicopathological parameters,Disease Free Survival Time（DSF） in human breast cancer.Methods：122 breast cancer paraffin-embedded tissue was made into chip.These patients not only underwent completely resected but also accepted standard chemotheray or radiotherapy who were enrolled from the first affiliated hospital,China Medical University.Immunohistochemical staining SP method was performed.DFS ranged from the date of operation to relaps or follow-up（July,2011）.There were 45 patients relaps.Results：The expression rate of COX-2 and HIF-1α was higher（58.2% 、51.6%） and the correlation between them was positive（r = 0.313,P = 0.001）.Expression of COX-2 was positive correlated with tumour size（r = 0.192,P = 0.034）,clinical stage（r = 0.193,P = 0.033）,lymph node metastasis（r = 0.186,P = 0.040）.Expression of HIF-1αwas positive correlated with tumour size（r = 0.345,P = 0.001）,clinical stage（r = 0.209,P = 0.037）,lymph node metastasis（r = 0.245,P = 0.002）.Expression of COX-2 or HIF-1αwas negative correlated with DFS by Kaplan-Meier survival analysis（P = 0.027,P = 0.034）.Conclusions：Over-expression of COX-2 and HIF-1α associated with a poor clinical outcome.In breast cancer HIF-1α possibly regulates expression of COX-2.