Originally published as JCO Early Release 10.1200/JCO.2005.00.471 on September 19 2005

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The TP53 Colorectal Cancer International Collaborative Study on the Prognostic and Predictive Significance of p53 Mutation: Influence of Tumor Site, Type of Mutation, and Adjuvant Treatment

From the Università di Palermo, Department of Oncology, Italy; University of Western Australia, Nedlands, Australia; University of Oxford, Department of Clinical Pharmacology, Oxford, United Kingdom; and Hôpital Tenon, Paris, France

Address reprint requests to Antonio Russo, MD, Via Veneto 5, 90144 Palermo, Italy; e-mail: Lab-oncobiologia{at}usa.net or molecularoncology{at}yahoo.it

PURPOSE: The aims of the TP53 Colorectal Cancer (CRC) International Collaborative Study were to evaluate the possible associations between specific TP53 mutations and tumor site, and to evaluate the prognostic and predictive significance of these mutations in different site, stage, and treatment subgroups.

PATIENTS AND METHODS: A total of 3,583 CRC patients from 25 different research groups in 17 countries were recruited to the study. Patients were divided into three groups according to site of the primary tumor. TP53 mutational analyses spanned exons 4 to 8.

RESULTS: TP53 mutations were found in 34% of the proximal colon tumors and in 45% of the distal colon and rectal tumors. They were associated with lymphatic invasion in proximal tumors. In distal colon tumors, deletions causing loss of amino acids were associated with worse survival. In proximal colon tumors, mutations in exon 5 showed a trend toward statistical significance (P < .05) when overall survival was considered. Dukes' C tumors with wild-type TP53 and those with mutated TP53 (proximal tumors) showed significantly better prognosis when treated with adjuvant chemotherapy.

CONCLUSION: Analysis of TP53 mutations from a large cohort of CRC patients has identified tumor site, type of mutation, and adjuvant treatment as important factors in determining the prognostic significance of this genetic alteration.

Supported by Ministero dell’Instruzione, dell’Universita e della Recerca/Programmi di Ricerca di Relevante Interes se Nazionale 2002 (prot. 2002068725); Progetto Speciale 2000 Ministero Sanità (Grant No. 100/SCPS/4/18306); and grants from Associazione Italiana per la Ricerca sul Cancro.

Members of the TP53-CRC Collaborative Group are found in the Appendix.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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