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p53 and K-ras Gene Mutations Correlate With Tumor Aggressiveness But Are Not of Routine Prognostic Value in Colorectal Cancer

From the Department of Cancer and Metastasis, Institut de Recerca Oncològica, Hospital Duran i Reynals; Department of Medical Oncology, Laboratori d'Investigació Gastrointestinal, Institut de Recerca; Department of Pathology, Hospital de Sant Pau; and Institut Català d'Oncologia, L'Hospitalet, Barcelona, Spain.

Address reprint requests to Gabriel Capellá, MD, Laboratori de Biologia Molecular, Institut Català d'Oncologia, Av Gran Via s/n, km 2.7, 08907 L'Hospitalet, Barcelona, Spain; email gcapella{at}ico.scs.es

PURPOSE: p53 gene and K-ras mutations are among the most common genetic alterations present in colorectal cancer. The prognostic utility of such mutations remains controversial. The purpose of this study was to prospectively evaluate the prognostic significance of p53 and K-ras gene mutations in colorectal cancer.

PATIENTS AND METHODS: One hundred forty patients were analyzed. Tumors belonging to the microsatellite mutator phenotype were excluded (n = 8). Mutations at the K-ras and p53 genes were detected and characterized by restriction fragment length polymorphism, single-strand conformation polymorphism, and sequencing, as appropriate.

RESULTS: p53 mutations were detected in 66 (50%) and K-ras mutations were detected in 54 (41%) of the 132 patients. In 26 cases (20%), ras and p53 mutations coexisted; in 38 cases (29%), neither mutation was found. Multivariate analysis of the whole population analyzed (n = 132) showed that survival was strongly correlated with the presence of p53 mutations alone or in combination with K-ras mutations (P = .002; log-rank test). When only patients undergoing a radical resection were considered (R0; n = 101), p53 mutations were no longer of prognostic significance.

CONCLUSION: p53 mutations alone or in combination with K-ras mutations are correlated with a worse outcome. However, the routine use of these mutations as prognostic markers in the clinical setting is not recommended.

R.A. and S.T. are fellows of the Spanish Ministry of Education and Science.

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