Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer
- R Jover1,
- P Zapater2,
- A Castells3,
- X Llor4,
- M Andreu5,
- J Cubiella6,
- V Piñol3,
- R M Xicola4,
- L Bujanda7,
- J M Reñé8,
- J Clofent9,
- X Bessa5,
- J D Morillas10,
- D Nicolás-Pérez11,
- A Payá12,
- C Alenda12,
- for the Gastrointestinal Oncology Group of the Spanish Gastroenterological Association
- 1Department of Gastroenterology. Hospital General Universitario de Alicante, Alicante, Spain
- 2Department of Clinical Pharmacology, Hospital General Universitario de Alicante, Alicante, Spain
- 3Department of Gastroenterology, Institut de Malaties Digestives, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
- 4Germans Trias i Pujol Hospital, Universitat Autonoma de Barcelona, Badalona, Spain
- 5Department of Gastroenterology, Hospital del Mar, Barcelona, Spain
- 6Department of Gastroenterology, Hospital Cristal Piñor, Orense, Spain
- 7Department of Gastroenterology, Hospital Donostia, San Sebastian, Spain
- 8Department of Gastroenterology, Hospital Arnau de Vilanova, Lleida, Spain
- 9Department of Gastroenterology, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
- 10Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain
- 11Department of Gastroenterology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
- 12Department of Pathology, Hospital General Universitario de Alicante, Alicante, Spain
- Correspondence to:
Dr R Jover
Gastroenterology Department, Hospital General Universitario de Alicante, C/ Pintor Baeza, sn 03010 Alicante, Spain; jover_
- Accepted 11 October 2005
- Revised 22 September 2005
- Published Online First 18 November 2005
Aim: Some retrospective studies have shown a lack of benefit of 5-fluorouracil (5-FU) adjuvant chemotherapy in patients with mismatch repair (MMR) deficient colorectal cancer. Our aim was to assess if this molecular marker can predict benefit from 5-FU adjuvant chemotherapy. A second objective was to determine if MMR status influences short term survival.
Methods: We included 754 patients with a median follow up of 728.5 days (range 1–1097). A total of 260 patients with stage II or III tumours received 5-FU adjuvant chemotherapy, according to standard clinical criteria and irrespective of their MMR status. A tumour was considered MMR deficient when either BAT-26 showed instability or there was loss of MLH1 or MSH2 protein expression.
Results: At the end of the follow up period, 206 patients died and 120 presented with tumour recurrence. Sixty six (8.8%) patients had MMR deficient tumours. There were no significant differences in overall survival (MMR competent 72.1%; MMR deficient 78.8%; p = 0.3) or disease free survival (MMR competent 61.3%; MMR deficient 72.3%; p = 0.08). In patients with stage II and III tumours, benefit from 5-FU adjuvant chemotherapy was restricted to patients with MMR competent tumours (overall survival: chemotherapy 87.1%; non-chemotherapy 73.5%; log rank, p = 0.00001). Patients with MMR deficient tumours did not benefit from adjuvant chemotherapy (overall survival: chemotherapy 89.5%; non-chemotherapy 82.4%; log rank, p = 0.4).
Conclusions: Benefit from 5-FU adjuvant chemotherapy depends on the MMR status of tumours in patients with colorectal cancer. 5-FU adjuvant chemotherapy improves survival in patients with MMR competent tumours but this benefit from chemotherapy cannot be extended to patients with MMR deficient tumours.
- MMR, mismatch repair
- 5-FU, 5-fluorouracil
- MSI, microsatellite instability
- TNM, tumour, node, metastases
Published online first 18 November 2005
This work was supported by grants from the Fondo de Investigación Sanitaria (FIS 01/0104) and from the Instituto de Salud Carlos III (RC03/02 and RC03/10). Xavier Llor is a recipient of a Ramon y Cajal grant from Ministerio de Ciencia y Tecnología of the Spanish government. Virgínia Piñol received a research grant from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS).
Conflict of interest: None declared.
All authors for the Gastrointestinal Oncology Group of the Spanish Gastroenterological Association are listed in the appendix.
This work was presented in part as a poster at the 2004 Digestive Diseases Week meeting, New Orleans, LA, USA.