Park Ji Won, Chang Hee Jin, Park Sohee, Kim Byung Chang, Kim Dae Yong, Baek Ji-Yeon, Kim Sun Young, Oh Jae Hwan, Choi Hyo Seong, Park Sung Chan, Jeong Seung-Yong
National Cancer Center, Goyang, Republic of Korea.
Ann Surg Oncol. 2010 Nov;17(11):2839-46. doi: 10.1245/s10434-010-1135-8. Epub 2010 Jun 12.
The predictive role of mismatch repair (MMR) status for survival after sporadic colorectal cancer remains a point of controversy. This study was designed to test the prognostic value of MMR status in sporadic colorectal cancers.
The study included 318 patients with sporadic colorectal cancer who underwent primary tumor resection. MMR status was determined by the immunohistochemical analysis of hMLH1 and hMSH2 expression.
Thirty-six carcinomas (11.3%) showed abnormal MMR protein expression (22 hMLH1 negative and 14 hMSH2 negative) and were classified as MMR-defective tumors. An MMR defect was strongly associated with a reduced likelihood of lymph node (odds ratio, 0.32; 95% confidence interval [95% CI], 0.13-0.75) or distant organ metastases at diagnosis (odds ratio, 0.07; 95% CI, 0.01-0.62), independent of the clinicopathological features. Overall survival was significantly better in patients with MMR-defective tumors than in those with MMR-intact tumors (P = 0.013). In the subgroup analysis by stage, adjusted for other potential confounding variables, MMR status was not a statistically significant prognostic factor in stage I and II patients, while the MMR defect predicted a significantly better overall survival in stage III and IV patients (adjusted hazard ratio, 0.23; 95% CI, 0.06-0.97; P = 0.045).
At initial diagnosis, metastases were found at lower rates in MMR-defective tumors. MMR status may be a stage-dependent prognostic factor in patients with sporadic colorectal cancer.
错配修复（MMR）状态对散发性结直肠癌患者生存的预测作用仍存在争议。本研究旨在检测MMR状态在散发性结直肠癌中的预后价值。
本研究纳入318例行原发性肿瘤切除术的散发性结直肠癌患者。通过免疫组化分析hMLH1和hMSH2表达来确定MMR状态。
36例癌（11.3%）显示MMR蛋白表达异常（22例hMLH1阴性，14例hMSH2阴性），被归类为MMR缺陷型肿瘤。MMR缺陷与诊断时淋巴结转移（比值比，0.32；95%置信区间[95%CI]，0.13 - 0.75）或远处器官转移的可能性降低密切相关（比值比，0.07；95%CI，0.01 - 0.62），与临床病理特征无关。MMR缺陷型肿瘤患者的总生存期显著优于MMR完整型肿瘤患者（P = 0.013）。在按分期进行的亚组分析中，校正其他潜在混杂变量后，MMR状态在I期和II期患者中不是具有统计学意义的预后因素，而MMR缺陷在III期和IV期患者中预测总生存期显著更好（校正风险比，0.23；95%CI，0.06 - 0.97；P = 0.045）。
在初始诊断时，MMR缺陷型肿瘤的转移发生率较低。MMR状态可能是散发性结直肠癌患者的一个分期依赖性预后因素。
