缺氧诱导因子1、血管内皮生长因子和环氧化酶-2在乳腺癌中表达的意义#br#

doi:10.3877/cma.j.issn.2095-655X.2014.04.008

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摘要目的研究缺氧诱导因子1（HIF-1α）、血管内皮生长因子（VEGF）、环氧化酶-2（COX-2）在乳腺癌中的表达与发生、发展及侵袭转移的关系。方法应用免疫组织化学S-P法检测61例乳腺癌前病变患者［25例导管非典型增生(ADH)、36例导管原位癌(DCIS）］和78例乳腺浸润性癌患者（IDC）组织中HIF-1α、VEGF和COX-2的表达情况，并与52例乳腺增生患者标本作为对照。采用SPSS17.0软件包，HIF-1α，VEGF和COX-2样本阳性率组间比较采用χ2检验。结果（1）HIF-1α、VEGF和COX-2在乳腺IDC中的阳性表达率分别为67.9%、64.1%和79.5%，明显高于在乳腺癌前病变（DCIS为44.4%、44.4%、55.6%；ADH为28.0%、32.0%、36.0%）和乳腺普通导管增生病变（7.7%，23.1%，15.4%）中的表达，差异有统计学意义（χ2=5.696,12.424,28.415;P<0.05）；（2）乳腺癌前病变中DCIS与ADH比较，HIF-1α（χ2=1.699，P>0.05）、VEGF（χ2=0.957，P>0.05）、COX2（χ2=2.263，P>0.05），差异无统计学意义；（3）HIF1α、VEGF和COX2在乳腺IDC中高表达与患者年龄（χ2=3.410,0.509,0.103;P>0.05）、肿瘤大小（χ2=2.010,0.143,0.304;P>0.05）无关，而与组织学分级（χ2=16.268,15.695,11.272;P<0.05））和淋巴转移（χ2=6.321,13.020,19.123；P<0.05）相关；（4）HIF-1α、VEGF和COX-2三者在乳腺癌中的表达呈正相关（r=0.263，χ2=5.412，P<0.05；r=0.436，χ2=9.441，P<0.05）。结论HIF-1α、VEGF和COX-2高表达是乳腺癌发生、侵袭转移行为的重要生物学标志，HIF-1α可能发生在癌变早期阶段，是乳腺癌的早起事件；VEGF和COX-2与乳腺癌进展期侵袭转移更相关；HIF-1α、VEGF和COX-2联合检测可作为判断乳腺癌预后的指标。

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关键词 ：乳腺肿瘤, 癌前状态, 缺氧诱导因子1, α亚基, 血管内皮生长因子类

Abstract：ObjectiveTo investigate the expression of HIF-1α,VEGF and COX-2 in breast carcinoma and their associations with the occurrence,development,invasion and metastasis of breast carcinoma.MethodsThe expression of HIF-1α,VEGF and COX-2 was detected by immunohistochemistry S-P method in sixty-one cases of precancerous lesions including twenty-five cases of atypical ductal hyperplasia (ADH),thirtysix cases of ductal carcinoma in situ (DCIS),and seventy-eight cases of invasive ductal carcinoma (IDC) of the breast.Twenty-six cases of hyperplasia breast tissues were selected as control group.The differences of positive rates of HIF-1α,VEGF and COX-2 were compared with chi-square test.ResultsThe positive rates of HIF-1α,VEGF and COX-2 in IDC were 67.9%,64.1% and 79.5% respectively;the positive rates in DCIS were 44.4%,44.4%,55.6% respectively,and the positive rates in ADH were 28.0%,32.0%,36.0% respectively,which were higher than those in hyperplasia breast tissues(7.7%,23.1%,15.4%,χ2=5.696,12.424,28.415;P<0.05).However,there were no significant differences in the positive expression rates of HIF-1α,VEGF and COX-2 between ADH and DCIS tissue (χ2=1.699,0.957,2.263;P>0.05).There was a correlation between overexpression of HIF-1α,VEGF and COX-2 with the histological grade and lymph node metastasis of IDC repectively,wherease without correlation with age and size of tumor (χ2=3.410,0.509,0.103;P>0.05).The expression of COX-2 was positively correlated with HIF-1α and VEGF(r=0.263,χ2=5.412,P<0.05; r=0.436, χ2=9.441,P<0.05).ConclusionsThe overexpression of HIF-1α,VEGF and COX-2 might be important biological markers for the invasion,lymph node metastasis and distant metastasis of IDC.The combined detection of HIF-1α,VEGF and COX-2 is a predictor for prognosis.

Key words： Breast neoplasms Precancerous conditions HIF-1α VEGF

收稿日期: 2014-08-01

基金资助:日照市应用技术研究与开发计划项目（2060402）；济宁医学院科研计划重点项目（JY2013KJ051）

通讯作者: 张作峰，Email：wgprzph93@163.com

引用本文:

张永刚张作峰许京中王刚平. 缺氧诱导因子1、血管内皮生长因子和环氧化酶-2在乳腺癌中表达的意义#br#[J]. 中华诊断学电子杂志, 2014, 2(4): 275-278.
Zhang Yonggang*,Zhou Xiaoyan,Wang Gangping,Zhang Zuofeng,Xu Jingzhong. #br# The expression and the clinical significance of HIF-1α,VEGF and COX-2 in breast carcinoma and precancerous lesions. zhzdx, 2014, 2(4): 275-278.

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