乳腺癌耐药蛋白ERCC1和P-gp表达水平与新辅助化疗敏感性关系研究

Correlation between expression of ERCC1 and P-gp and sensitivity of neoadjuvant chemotherapy in breast cancer

目的:研究耐药蛋白ERCC1和P-gp在乳腺癌中表达与临床病理特征的联系;分析ERCC1和P-gp的不同表型与新辅助化疗敏感性的相关性;探讨依据ERCC1和P-gp的不同表型制定乳腺癌化疗方案的可行性。方法:用免疫组化回顾性检测56例乳腺癌新辅助化疗前穿刺活检留取的石蜡标本中ERCC1和P-gp的表达情况,分析两者与乳腺癌临床病理特征的关系,乳腺癌不同受体分型与化疗敏感性的关系;以及ERCC1和P-gp不同表型间新辅助化疗敏感性的差异。结果:ERCC1阳性表达率为35.7%(20/56),P-gp阳性表达率为44.6%(25/56),两者表达无明显相关性(χ~2=2.969,P=0.085)。ERCC1表达水平与肿瘤大小和TNM分期呈负相关,而P-gp则表达水平升高肿瘤分级越高。乳腺癌Luminal型、三阴性和Her-2阳性三者间比较,分别是Her-2阳性组CR率(47.1%)和三阴性pCR率(25.0%)最高,但Her-2阳性与三阴性的CR和p CR率均无统计学差异。耐药蛋白ERCC1和P-gp均为阴性者有效率(CR+PR,87.0%)最高,ERCC1阴性者有效率(72.2%)较ERCC1阳性者有效率(45.0%)高;P-gp阴性者有效率(80.6%)较P-gp阳性者有效率(40.0%)高。结论:ERCC1和P-gp是两个相对独立的耐药蛋白,两者表达阴性时乳腺癌新辅助化疗有效率更高。通过检测肿瘤组织中ERCC1和P-gp的表达情况,联合ER、PR和Her-2等分子指标,可以预测化疗敏感性和规避潜在的耐药,个体化的制定化疗方案。

Objective To investigate the correlation between expression of resistance protein ERCC1 and P-gp and breast cancer clinical and pathological features; to analyze the relationship between different phenotype of ERCC1 and P- gp and sensi-tivity of neoadjuvant chemotherapy ; to explore the feasibility that according ERCC1 and P -gp phenotype to determine the chem-otherapy regime for breast cancer. Method A retrospective study that use immunohistochemical detect 56 cases biopsy specimens of breast cancer who undergo neoadjuvant chemotherapy, to analyze the relationship between ERCC1 and P-gp expression and both of clinical and pathological features of breast cancer, relationship between different breast cancer receptor sub - type and chemotherapy sensitivity;and relationship between ERCC1 and the P-gp phenotype and neoadjuvant chemotherapy sensitivi-ty. Results ERCC1 positive expression rate was 35.1% （2 0 /5 6 ） ,P - gp positive expression rate was 44. 6% （2 5 /5 6 ） , no sig-nificant correlation between the expression （χ^2= 2 . 9 6 9 ,P =0. 08 5 ）. ERCC1 expression levels and tumor size and TNM staging was a negative correlation, while the P-gp expression levels were higher in high tumor grade. To compare luminal type of breast cancer, triple negative and Her-2 positive type, Her -2 positive group CR rate （47. 1% ） and three negative group pCR rate （25. 0% ） were the highest,but Her -2 positive and triple negative was no significant difference in CR rate and pCR rate. The ef-fective rate （CR ＋ PR,87. 0% ）was the highest in drug resistance protein ERCC1 and P-gp both negative,the effective rate of ERCC1 negative（72. 2% ） was higher than that in ERCC1 positive （45. 0% ） ;the effective rate of P - gp negative（80. 6% ） was higher than that in P - gp - positive （40. 0% ）. Conclusion ERCC1 and P - g p are two relatively independent drug - resistance protein,the effective rate of neoadjuvant chemotherapy in breast cancer is higher when both were negative expression. By detected ERCC1 and P-gp expression in tumor tissue,and combine ER,PR and Her -2 and other molecular indicators,we can predict chemotherapy sensitivity, and to avoid resistance possible, then to perform a individualized chemotherapy.