The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status Rodrigo Jover a, * , Pedro Zapater b , Antoni Castells c , Xavier Llor d,m , Montserrat Andreu e , Joaquı´n Cubiella f , Francesc Balaguer c , Laura Sempere a , Rosa M. Xicola d,m , Luis Bujanda g , Josep M. Ren ˜e ´ h , Juan Clofent i , Xavier Bessa e , Juan D. Morillas j , David Nicola ´ s-Pe ´rez k , Elisenda Pons d , Artemio Paya ´ l , Cristina Alenda l , Gastrointestinal Oncology Group of the Spanish Gastroenterological Association n a Unidad de Gastroenterologı ´a, Hospital General Universitario de Alicante, Alicante, Spain b Department of Clinical Pharmacology, Hospital General Universitario de Alicante, Alicante, Spain c Department of Gastroenterology, Institut de Malaties Digestives, Hospital Clı´nic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain d Germans Trias i Pujol Hospital, Universitat Autonoma de Barcelona, Badalona, Spain e Department of Gastroenterology, Hospital del Mar, Barcelona, Spain f Department of Gastroenterology, Hospital Cristal Pin ˜or, Orense, Spain g Department of Gastroenterology, Hospital Donostia, CIBERehd, San Sebastian, Spain h Department of Gastroenterology, Hospital Arnau de Vilanova, Lleida, Spain i Department of Gastroenterology, Complejo Hospitalario Universitario de Vigo, Vigo, Spain j Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain k Department of Gastroenterology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain l Department of Pathology, Hospital General Universitario de Alicante, Alicante, Spain m Digestive Diseases and Nutrition Section, University of Illinois at Chicago, Chicago IL, USA ARTICLE INFO Article history: Received 8 May 2008 Received in revised form 30 June 2008 Accepted 1 July 2008 Available online 21 August 2008 Keywords: Colorectal cancer Treatment Microsatellite instability 5-Fluorouracil Prognosis 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 insta- bility 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 adju- vant chemotherapy (log-rank p = 0.7). A multivariate analysis showed an independent 0959-8049/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2008.07.016 * Corresponding author: Tel.:+34 965938345; fax: +34 965938355. E-mail address: jover_rod@gva.es (R. Jover). n All authors are listed in Appendix. EUROPEAN JOURNAL OF CANCER 45 (2009) 365 – 373 available at www.sciencedirect.com journal homepage: www.ejconline.com