结直肠癌组织中ERCC1和BRCA1的表达及其与铂类化疗疗效的相关性

摘要

目的 探讨结直肠癌组织中核苷酸切除修复交错互补基因1(excision repair cross-complementing gene 1，ERCC1)及乳腺癌易感基因1(breast cancer susceptibility gene 1，BRCA1)的表达及其临床意义。方法 采用免疫组化的方法检测结直肠癌组织中ERCC1及BRCA1蛋白的表达水平。结果 结直肠癌组织中ERCC1阳性表达率为43.1％；ERCC1表达与组织病理学分级有关；ERCC1阴性患者术后应用奥沙利铂为主的方案化疗后，中位生存期(median survival time，MST)高于阳性患者，两者间差异有统计学意义(P=0.013)。结直肠癌组织中BRCA1阳性表达率为52.8％；BRCA1表达与组织病理学分级有关；BRCA1阴性患者术后应用奥沙利铂为主的方案化疗后，MST高于阳性患者,两者间差异无统计学意义(P=0.16)。ERCC1和BRCA1均为阴性的患者术后应用奥沙利铂为主的方案化疗后，MST高于ERCC1和BRCA1均为阳性的患者，两者间差异有统计学意义(P=0.025)。ERCC1和BRCA1的表达在结直肠癌中有显著的正相关性(r=0.485，P=0.007)。结论 ERCC1阴性患者应用奥沙利铂为主的方案化疗可获得生存受益，但BRCA1阴性患者生存获益不明显；ERCC1和BRCA1的表达水平有可能作为结直肠癌患者术后辅助化疗方案的选择及预后判断的指标。%Objective To explore the expressions of excision repair cross-complementing gene 1 (ERCC1) and breast cancer susceptibility gene 1 (BRCA1) in the tissues of colorectal cancer and its clinical significance. Methods ERCC1 and BRCA1 expressions in the tissues of colorectal cancer were measured by immunohistochemistry. Results The positive rate of ERCC1 expression was 43.1%, and was significantly correlated with histologic grade. Compared with ERCC1 positive patients, ERCC1 negative patients had longer median survival time (MST) with statistical difference (P = 0.013). The positive rate of BRCA1 expression was 52.8% ,and was significantly correlated with histologic grade. Compared with BRCA1 positive patients, BRCA1 negative patients had longer MST, but the difference was not significant (P = 0.16) . Compared with ERCC 1 positive plus BRCA 1 positive patients,ERCC1 negative plus BRCA1 negative patients had significantly longer MST (P = 0.025). The positive expression of ERCC1 and BRCA1 had a significant positive correlation with colorectal cancer (r = 0.485, P = 0.007). Conclusions ERCC1 negative patients with oxaliplatin-based chemotherapy may obtain survival benefit, but the survival benefit in BRCA1 negative patients was not obvious. Expression levels of ERCC1 and BRCA1 might be useful in the choice of chemotherapy regimes and evaluation of prognosis for patients with colorectal cancer after surgery.