Abstract
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.
Keywords
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Article info
Publication history
Published online: August 26, 2008
Accepted:
July 1,
2008
Received in revised form:
June 30,
2008
Received:
May 8,
2008
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
