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Annals of Oncology Advance Access published online on October 15, 2009
Annals of Oncology, doi:10.1093/annonc/mdp383
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Impact of p53 expression and microsatellite instability on stage III colon cancer disease-free survival in patients treated by 5-fluorouracil and leucovorin with or without oxaliplatin

A. Zaanan1,2,3, P. Cuilliere-Dartigues1,2,4, A. Guilloux1,2, Y. Parc1,2,5, C. Louvet1,2,3, A. de Gramont1,2,3, E. Tiret2,5, S. Dumont6, B. Gayet7, P. Validire8, J.-F. Fléjou1,2,4, A. Duval1,2 and F. Praz1,2,*

1 INSERM, UMR_S 938, Saint-Antoine Research Centre
2 UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre
3 Department of Medical Oncology, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris
4 Department of Pathology, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris
5 Department of General and Digestive Surgery, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris
6 Institut Fédératif de Recherche65, UPMC Univ Paris 06
7 Department of Digestive Disease Medical Surgery, Institut Mutualiste Montsouris, University Paris Descartes, Paris, France
8 Department of Pathology, Institut Mutualiste Montsouris, University Paris Descartes, Paris, France

* Correspondence to: Dr F. Praz, INSERM UMR_S 938-UPMC, 184 rue du Faubourg Saint-Antoine, 75571 Paris cedex 12, France. Tel: +33-149-284-609; Fax: +33-149-286-681; E-mail: francoise.praz{at}upmc.fr

Background: The aim was to determine the values of p53 tumour expression and microsatellite instability (MSI) phenotype to predict benefit from adjuvant chemotherapy of colon cancer by 5-fluorouracil and leucovorin (FL) alone or with oxaliplatin (FOLFOX).

Patients and methods: This retrospective study included 233 unselected patients with stage III colon cancer treated by FL (n = 124) or FOLFOX (n = 109). The impact of p53 expression and MSI on disease-free survival (DFS) was defined using univariate and multivariate analyses. A Cox proportional hazards model was specifically designed to evaluate the interaction between chemotherapy and these genetic alterations.

Results: In univariate analyses, addition of oxaliplatin significantly improved DFS provided that tumour overexpressed p53 [hazard ratio (HR) 0.39; 95% confidence interval (CI) 0.19–0.82; P = 0.01] or displayed MSI phenotype (HR 0.17; 95% CI 0.04–0.68; P = 0.01). In multivariate analyses, p53 was confirmed as an independent factor predictive of benefit from FOLFOX (P = 0.03), while the interaction of MSI with chemotherapy could not be determined in the absence of relapse in the MSI group treated with FOLFOX.

Conclusion: Our observations indicate that MSI status and p53 expression may influence the impact of oxaliplatin on adjuvant treatment of stage III colon cancer patients.

chemotherapy, colon cancer, disease-free survival, microsatellite instability, oxaliplatin, p53

Received for publication April 3, 2009. Revision received June 29, 2009. Accepted for publication July 1, 2009.


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