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  • Title: 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.
    Author: Zaanan A, Cuilliere-Dartigues P, Guilloux A, Parc Y, Louvet C, de Gramont A, Tiret E, Dumont S, Gayet B, Validire P, Fléjou JF, Duval A, Praz F.
    Journal: Ann Oncol; 2010 Apr; 21(4):772-780. PubMed ID: 19833818.
    Abstract:
    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.
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