Prognostic Significance of the Mismatch Repair Gene in Colorectal Cancer Patients Treated with 5-Fluorouracil Chemotherapy.

Abstract

Objective: To correlate mismatch repair gene defects with the outcomes of colorectal carcinoma patients having undergone adjuvant chemotherapy containing 5-fluorouracil. Material and Methods: The records of all stage II, III and IV colorectal carcinoma cases treated at Songklanagarind Hospital from 1994-2003 were examined for the study. There were 140 patients and all had received adjuvant 5-fluorouracil-based chemotherapy. The mismatch repair gene proteins mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1) and mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2) in tumor cells were evaluated by immunohistochemistry. Negative staining confirmed abnormalities in or complete loss of mismatch repair genes. Survival analysis was carried out using the Kaplan-Meier method and the Cox Proportional Hazards regression. Results: Mismatch repair gene defects were detected in 36 cases (25.7%): only MLH1 defects in 15 cases (10.7%), only MSH2 defects in 10 cases (7.1%), and both MLH1 and MSH2 defects in 11 cases (7.8%). Survival analysis showed no significant differences between mutated mismatch repair gene patients and normal mismatch repair gene patients (95% CI=0.35 to 0.67, p=0.54). Conclusion: Mismatch repair gene defects do not predict the prognosis of colorectal cancer patients treated with 5-fluorouracil-based chemotherapy.

Keywords

• 5-fluorouracil, colorectal cancer, mismatch repair gene, mlh1 and msh2