凋亡相关基因bcl-2基因族在乳腺癌中的预后作用

Prognostic Significance of Apoptosis Related Gene Family bcl 2 in Human Breast Cancer Tissues

探讨癌基因ｂｃｌ－２及其基因族成员ｂａｘ、ｂｃｌｘ的表达水平与乳腺癌生物学行为的关系及对乳腺癌预后的意义。方法运用免疫组化方法对９１例乳腺癌石蜡组织切片ｂｃｌ－２、ｂａｘ蛋白表达水平进行检测，运用Ｎｏｒｔｈｅｒｎ印迹法检测１６例新鲜乳腺癌组织标本ｂｃｌｘｌｍＲＮＡ表达水平。结果９１例乳腺癌病例中，ｂｃｌ２阳性率６５．９％（６０／９１），ｂａｘ阳性率６４．８％（５９／９１）。ｂｃｌ２、ｂａｘ蛋白表达水平与凋亡指数（ＡＩ）、病理组织学分级、腋淋巴结转移情况、术后局部复发与转移相关，ｂｃｌ２表达与雌激素受体（ＥＲ）水平正相关。ＡＩ与ｂｃｌ２、ｂａｘ蛋白表达水平相关。对影响乳腺癌术后无病生存率的单因素分析结果显示，ｂｃｌ２、ｂａｘ蛋白表达水平具有预后作用；Ｃｏｘ’ｓ模型多因素分析结果，ｂｃｌ２蛋白表达水平是独立的预后指标。１６例乳腺癌新鲜标本中，５０％（８／１６）ｂｃｌｘｌｍＲＮＡ高表达，其表达水平与ｂｃｌ２蛋白表达、腋淋巴结转移相关。结论凋亡相关基因ｂｃｌ２、ｂａｘ、ｂｃｌｘｌ表达失调可导致乳腺癌细胞凋亡调控的紊乱，使腋淋巴结转移程度增加。

Purpose To study the prognostic effect of bcl 2 oncogene and its gene family members bax,bcl x expression in breast cancer patients. Methods In 91 human breast cancer tissue sections, we studied the immunohistochmical expression of bcl 2,bax proteins.Using Northern blot method, we detected bcl xl mRNA expression in frozen tissues from 16 breast cancer patients. Results bcl 2 protein positivity was found in 60/91(65.9%) patients, and bax positivity 59/91(64.8%).bcl 2 and bax expression levels were associated with apoptotic index(AI),histological grade,axillary lymph node metastasis,postoperative local reccurence and metastasis.bcl 2 expression was related to estrogen receptor(ER) positivity.In univariate analysis for disease free survival(DFS),bcl 2 and bax protein levels,AI were found to have prognostic value.The result of Cox's model multivariate analysis showed that bcl 2 protein level was an independent prognostic factor.In 16 frozen breast cancer tissues,8/16(50%) had higher level of bcl xl mRNA,which showed correlation with bcl 2 protein expression and axillary lymph node metastasis. Conclusions Our findings indicate that dysregulated expressions of bcl 2,bax and bcl xl apoptosis related genes, suggestive of serious deregulation of apoptotic process,may contribute to the biologic aggresiveness of breast cancer.bcl 2 protein is an independent indicator of prognosis in breast cancer patients.