p53 and K-ras gene mutations correlate with tumor aggressiveness but are not of routine prognostic value in colorectal cancer

Purpose: p53 gene and K-ras mutations are among the most common genetic alt erations present in colorectal cancer. The prognostic utility of such mutat ions remains controversial. The purpose of this study was to prospectively evaluate the prognostic significance of p53 and K-ras gene mutations in col orectal cancer. Patients and Methods: One hundred forty patients were analyzed. Tumors belo nging to the microsatellite mutator phenotype were excluded (n = 8). Mutati ons at the K-ras and p53 genes were detected and characterized by restricti on fragment length polymorphism, single-strand conformation polymorphism, a nd sequencing, as appropriate. Results: p53 mutations were detected in 66 (50%) and K-ras mutations were d etected in 54 (41%) of the 132 patients. In 26 cases (20%), ras and p53 mut ations coexisted; in 38 cases (29%), neither mutation was found. Multivaria te analysis of the whole population analyzed (n = 132) showed that survival was strongly correlated with the presence of p53 mutations alone or in com bination with K-ros 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 mutation s as prognostic markers in the clinical setting is not recommended. J Clin Oncol 17:1375-1381. (C) 1999 by American Society of Clinical Oncology.