Lanza Giovanni, Gafà Roberta, Santini Alessandra, Maestri Iva, Guerzoni Laura, Cavazzini Luigi
Department of Experimental and Diagnostic Medicine, Section of Anatomic Pathology, University of Ferrara, Ferrara, Italy.
J Clin Oncol. 2006 May 20;24(15):2359-67. doi: 10.1200/JCO.2005.03.2433.
To evaluate the prognostic significance of DNA mismatch repair (MMR) status in a large series of stage II and III colorectal cancer patients. The relationship among MMR status, adjuvant chemotherapy, and clinical outcome was also investigated.
The study included 718 patients with colorectal adenocarcinoma (393 stage II and 325 stage III) who underwent curative surgical resection. MMR status was determined by immunohistochemical analysis of MLH1 and MSH2 expression. Microsatellite instability (MSI) was assessed in 363 patients using mononucleotide and dinucleotide markers.
One hundred fourteen (15.9%) carcinomas showed abnormal MMR protein (MMRP) expression (96 MLH1 negative and 18 MSH2 negative) and were classified as MMRP negative, whereas 604 tumors demonstrated normal MLH1/MSH2 immunoreactivity (MMRP positive). MLH1/MSH2 expression was closely related to MSI status (P < .001) and several clinicopathologic features. Patients with MMRP-negative carcinomas demonstrated a marked reduction in the risk of cancer-related death with respect to patients with MMRP-positive tumors (hazard ratio, 0.2579; 95% CI, 0.1289 to 0.5159). A better clinical outcome for patients with MMRP-negative tumors was observed in both stage II (P = .0006) and stage III (P = .0052) disease. In stage III disease, the survival advantage conferred by MMRP-negative tumors was more evident among patients treated with surgery alone than among patients who received adjuvant chemotherapy. A nonsignificant trend for survival benefit from adjuvant chemotherapy was observed among patients with MMRP-positive carcinomas but not among those with MMRP-negative carcinomas.
Immunohistochemical testing for MLH1/MSH2 expression provides useful prognostic information for the management of stage II and III colorectal cancer patients.
评估大量II期和III期结直肠癌患者中DNA错配修复（MMR）状态的预后意义。同时研究MMR状态、辅助化疗与临床结局之间的关系。
本研究纳入718例行根治性手术切除的结直肠腺癌患者（393例II期和325例III期）。通过对MLH1和MSH2表达进行免疫组化分析来确定MMR状态。使用单核苷酸和二核苷酸标记物对363例患者评估微卫星不稳定性（MSI）。
114例（15.9%）癌显示MMR蛋白（MMRP）表达异常（96例MLH1阴性和18例MSH2阴性），被分类为MMRP阴性，而604例肿瘤显示MLH1/MSH2免疫反应性正常（MMRP阳性）。MLH1/MSH2表达与MSI状态（P < 0.001）及多个临床病理特征密切相关。与MMRP阳性肿瘤患者相比，MMRP阴性癌患者的癌症相关死亡风险显著降低（风险比，0.2579；95%可信区间，0.1289至0.5159）。在II期（P = 0.0006）和III期（P = 0.0052）疾病中，均观察到MMRP阴性肿瘤患者有更好的临床结局。在III期疾病中，MMRP阴性肿瘤带来的生存优势在单纯接受手术治疗的患者中比接受辅助化疗的患者中更明显。在MMRP阳性癌患者中观察到辅助化疗有生存获益的趋势，但在MMRP阴性癌患者中未观察到。
对MLH1/MSH2表达进行免疫组化检测可为II期和III期结直肠癌患者的管理提供有用的预后信息。
