HIF-1α、Notch1及上皮间质转化在乳腺癌中的表达及意义

Significance of the expression of HIF-1α,Notch1 and EMT in breast carcinoma

目的探讨缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、Notch1与上皮间质转化(epithelial-mesenchymal transition,EMT)免疫表型在乳腺浸润性导管癌中的表达及临床意义。方法采用免疫组化法,检测乳腺浸润性导管癌(60例)和癌旁正常乳腺组织(20例)中HIF-1α、Notch1及EMT免疫表型E-钙粘蛋白(E-cadherin)、波形蛋白(Vimentin)的表达。结果 HIF-1α、Notch1、E-cadherin、Vimentin在乳腺癌组织中的表达阳性率分别为78.3%、81.7%、75%、33.3%,与癌旁正常乳腺组织中表达(阳性率分别为10%、20%、100%、0%)差异具有统计学意义(P<0.05);HIF-1α、Notch1、E-cadherin、Vimentin的表达与浸润性导管癌组织学分级、腋窝淋巴结转移及临床分期密切相关(P<0.05)。HIF-1α的表达与Notch1、Vimentin的表达呈正相关关系(P<0.05),而与E-cadherin的表达呈负相关关系(r=-0.545,P<0.05)。结论 HIF-1α通过上调Notch1、Vimentin的表达,下调E-cadherin的表达,促进乳腺浸润性导管癌EMT的发生,并促进癌组织的转移。联合检测HIF-1α、Notch1、E-cadherin、Vimentin的表达可成为判断乳腺癌生物学行为及转移情况的重要参考指标。

Objective To investigate the significance of the expression of HIF-1α,Notchl and EMT in invasive ductal carcino ma of breast. Methods Immunohistochemical method was used to detect the expression of HIF-1α,Notchl,E-cadherin and Vi- men, in in 60 cases of invasive ductal carcinoma of breast and 20 cases of normal breast tissues adjacent to carcinoma. Results The positive expression rates of HIF-1α,Notchl, E-cadherin and vimentin was 78.3%, 81.7%, 75% and 33.3% in breast cancer tissues, respectively, which were significant differences as compared with the expression in normal breast tissues adjacent to carcinoma （P〈0.05）. The expression of HIF-la, Notch1, E-cadherin and Vimentin were correlated with histological grade and axillary lymph node metastasis and clinical stage （P〈0.05）. There is a positive correlation between the expression of HIF- 1 α and Notehl, Vimentin. However, there was negative correlation between the expression of HIF-1 α and E-cadherin. Conclusion The expression of HIF-1α, Notchl and EMT was found to be related with the invasion and immigration of invasive ductal car- cinoma of breast. Combined detection of the expression of HIF-1α,Notchl ,E-cadherin and vimentin may be an important refer ence index of behavior biology and metastasis of breast carcinoma.