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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.

Original publication

DOI

10.1200/JCO.2005.00.471

Type

Journal article

Journal

J Clin Oncol

Publication Date

20/10/2005

Volume

23

Pages

7518 - 7528

Keywords

Adenocarcinoma, Mucinous, Aged, Antineoplastic Combined Chemotherapy Protocols, Chemotherapy, Adjuvant, Colorectal Neoplasms, DNA Mutational Analysis, Exons, Female, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Mutation, Neoplasm Invasiveness, Neoplasm Staging, Survival Rate, Tumor Suppressor Protein p53