Prognostic And Predictive Roles Of DNA Mismatch Repair Status In Stage Ⅱ/Ⅲ Colon Cancer And Multivariate Cox Analysis Of Prognostic Factors After Radical Resection

Purpose To analyse the prognostic and predictive roles of defective DNA mismatch repair (MMR) status and the clinicopathologic factors related to recurrence and metastasis of stage Ⅱ/Ⅲ colon cancer after radical resection.Methods The clinical and pathological data of628patients with stage Ⅱ/Ⅲ colon cancer under radical resection from Jan.2005to Dec.2008were retrospectively reviewed and analyzed. Immunohistochemistry for MMR proteins (MLH1,MSH2,MSH6and PMS2) were performed on440patients.Results Overall,90(20.5%) of440patients exhibited defective DNA mismatch repair (dMMR). The prognostic analyses showed increased disease-free survival (DFS) and overall survival (OS) for dMMR patients versus pMMR patients (P=0.018and P=0.015). Adjuvant therapy significantly improved OS in patients with pMMR tumors(P=0.018), but showed no difference in DFS(P=0.124). Patients with dMMR tumors receiving adjuvant chemotherapy (5-Fu/LV or FOLFOX) had no improvement in DFS (P=0.674) and OS (P=0.981) compared with those assigned to surgery alone. In patients with dMMR tumors, treatment with5-Fu/LV was associated with reduced disease-free survival (DFS) compared with those assigned to surgery alone or treatment with FOLFOX (P=0.022). Univariate analysis showed that age, depth of tumor invasion, lymphatic invasion, histological differentiation and MMR status were correlated to recurrence and metastasis of colon cancer after radical resection. Multivariate analysis showed that T4, lymphatic invasion, surgery alone and pMMR were independent factors affecting the prognosis of patients with colon cancer.Conclusion Colon cancer with dMMR have a better prognosis than with pMMR and may do not have the same response to adjuvant chemotherapy compared with pMMR. These data support MMR status assessment for patients being considered for FU therapy alone and consideration of MMR status in treatment decision making. T4, lymphatic invasion, surgery alone and pMMR were independent factors affecting the prognosis of patients with colon cancer.