AIMS: The aim of this study is to evaluate if mismatch repair (MMR) defective colorectal cancer has a different response to adjuvant 5-fluorouracil (5-FU) chemotherapy in a cohort of patients prospectively followed during 5 years. METHODS: The cohort included 754 surgically treated patients with colorectal cancer. MMR status was diagnosed by MLH1 and MSH2 immunohistochemistry and microsatellite instability analysis. Median follow-up was 49.2 months (range 1-73). At inclusion, 505 patients were diagnosed as TNM II or III stage, analysis of the efficacy of adjuvant chemotherapy was made on this population. Adjuvant chemotherapy was applied to 248 patients (98.2% 5-FU based). RESULTS: MMR deficiency was found in 76 patients (10.1%). No differences were found in overall survival (log-rank p=0.3) or disease-free survival (log-rank p=0.3) regarding MMR status. Adjuvant chemotherapy improves survival in patients in the II or III stage, but this improvement is only evident in patients with MMR-competent tumours (log-rank p=0.00001). Survival of patients with MMR-defective tumours does not improve with adjuvant chemotherapy (log-rank p=0.7). A multivariate analysis showed an independent effect of the interaction between MMR status and adjuvant chemotherapy (Hazard ratio 2.04; 95% confidence interval: 1.42-2.93). CONCLUSION: In a cohort of colorectal cancer patients, those with MMR-deficient tumours seem not to benefit from 5-FU-based chemotherapy.
AIMS: The aim of this study is to evaluate if mismatch repair (MMR) defective colorectal cancer has a different response to adjuvant 5-fluorouracil (5-FU) chemotherapy in a cohort of patients prospectively followed during 5 years. METHODS: The cohort included 754 surgically treated patients with colorectal cancer. MMR status was diagnosed by MLH1 and MSH2 immunohistochemistry and microsatellite instability analysis. Median follow-up was 49.2 months (range 1-73). At inclusion, 505 patients were diagnosed as TNM II or III stage, analysis of the efficacy of adjuvant chemotherapy was made on this population. Adjuvant chemotherapy was applied to 248 patients (98.2% 5-FU based). RESULTS:MMR deficiency was found in 76 patients (10.1%). No differences were found in overall survival (log-rank p=0.3) or disease-free survival (log-rank p=0.3) regarding MMR status. Adjuvant chemotherapy improves survival in patients in the II or III stage, but this improvement is only evident in patients with MMR-competent tumours (log-rank p=0.00001). Survival of patients with MMR-defective tumours does not improve with adjuvant chemotherapy (log-rank p=0.7). A multivariate analysis showed an independent effect of the interaction between MMR status and adjuvant chemotherapy (Hazard ratio 2.04; 95% confidence interval: 1.42-2.93). CONCLUSION: In a cohort of colorectal cancerpatients, those with MMR-deficient tumours seem not to benefit from 5-FU-based chemotherapy.
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Authors: Mine S Cicek; Noralane M Lindor; Steven Gallinger; Bharati Bapat; John L Hopper; Mark A Jenkins; Joanne Young; Daniel Buchanan; Michael D Walsh; Loic Le Marchand; Terrilea Burnett; Polly A Newcomb; William M Grady; Robert W Haile; Graham Casey; Sarah J Plummer; Lisa A Krumroy; John A Baron; Stephen N Thibodeau Journal: J Mol Diagn Date: 2011-05 Impact factor: 5.568
Authors: Wilfredo E De Jesus-Monge; Carmen Gonzalez-Keelan; Ronghua Zhao; Stanley R Hamilton; Miguel Rodriguez-Bigas; Marcia Cruz-Correa Journal: Fam Cancer Date: 2010-06 Impact factor: 2.375
Authors: Long Shan Li; Julio C Morales; Martina Veigl; David Sedwick; Sheldon Greer; Mark Meyers; Mark Wagner; Richard Fishel; David A Boothman Journal: Br J Pharmacol Date: 2009-09-23 Impact factor: 8.739