绝经前乳腺癌患者肿瘤组织中AIB-1蛋白表达与他莫昔芬耐药关系的研究

Relationship between AIB-1 and Tamoxifen Resistance in Premenopausal Patients with Primary Breast Cancer

目的:探讨绝经前乳腺癌患者肿瘤组织中AIB-1蛋白表达与他莫昔芬耐药关系。方法:选取2004年1月至2004年12月河北医科大学第四医院外一科手术切除并经病理证实、且随访资料完整的绝经前女性原发性乳腺癌206例,按照免疫组化检测结果分成:ER+/PR+且接受他莫昔芬治疗组(Tamoxifen group,T组),ER-PR-的非内分泌治疗组(Contol group,C组);T组及C组均按AIB-1及Her-2表达状态分为不同亚组。采用Kaplan-Meier法分析各组别无病生存(disease-free survival,DFS)及总生存(overallsurvival,OS)时间。结果:术后随访30～84个月,中位时间65个月,58例患者出现局部复发或远位转移,5年DFS为71.84%(148/206);死亡36例,5年OS为82.52%(170/206)。随着组织学分级、腋淋巴结阳性及Her-2蛋白表达的增高,AIB-1蛋白呈现高表达(x^2=12.573,P=0.002;x^2=7.939,P=0.005;x^2=4.502,P=0.036);分层分析中,T组AIB-1及Her-2均高表达亚组的DFS和OS低于其他亚组,且有统计学差异(x^2=5.900,P=0.002;x^2=4.533,P=0.049);该亚组患者的生存曲线明显低于其他亚组患者(Log-rank检验,x^2=8.903,P=0.005;x^2=9.405,P=0.004)。结论:AIB-1蛋白高表达常常伴随着不良的临床生物学行为和预后,AIB-1蛋白高表达、同时伴有Her-2高表达的绝经前乳腺癌患者对他莫昔芬治疗耐药,提示AIB-1的表达可以作为预测他莫昔芬耐药的因子。

Objective： To investigate the relationship between the protein expression of amplified breast cancer 1 （ AIB-1 ） and tamoxifen resistance in premenopausal patients with primary breast cancer. Methods： A total of 206 premenopausal patients with breast cancer were chosen for the study. The patients were diagnosed by pathology and were treated in The Fourth Hospital of Hebei Medical University. The estrogen and progestogen receptors as well as AIB-1 were analyzed by immunohistochemistry （ IHC ）. All cases were divided into two groups： the group of ER or PR positive, in which patients accepted tamoxifen therapy （ treatment group, group T ） and the group of both ER and PR negative, in which no endocrine treatment was given （ control group, group C ）. Group T and group C were divided into several subgroups according to their AIB-1 and HER-2 expression status. The disease-free survival （ DFS ） and overall survival （ OS ） rates were analyzed using Kaplan-Meier methods. Results： All cases were followed up from 30 months to 84 months, and the mean time was 65 months. A total of 58 patients experienced local recurrence and metastasis, while 36 of them died. The DFS and OS of 5 years were 71.84% （ 148/ 206 ） and 82.52% （ 170/206 ）, respectively. High AIB-1 expression was correlated with the histologic grade 3, axillary lymph nodes metastases and over-expression of HER-2 （ χ2 = 12.573, P = 0.002; χ2 =7.939, P = 0.005; χ2 = 4.502, P = 0.036）. The DFS and OS in the subgroup of both AIB-1 and HER-2 over-expression were lower than that of the other subgroups （ χ2 = 5.900, P = 0.002; χ2 = 4.533, P = 0.049 ）, and the survival was lower than that of the other subgroups （ Log-rank test,χ2 = 8.903, P - 0.005; Log-rank test, χ2=- 9.405, P = 0.004 ）. Conclusion： High AIB-1 is correlated with worse clinical biological behavior and prognosis. HER-2 over-expression, as well as high A1B-1 resulted in tamoxifen resistance for premenopausal patients with primary breast cancer. This condition implies that high AIB-1 may be an independent predictive factor of improved response to tamoxifen and may not be a factor that can predict tamoxifen resistance.