K-ras and p16 Aberrations Confer Poor Prognosis in Human Colorectal Cancer
Adult
Aged, 80 and over
Chromosome Aberrations
Male
0303 health sciences
Genes, p16
DNA Mutational Analysis
Adenocarcinoma
DNA Methylation
Middle Aged
Genes, p53
Prognosis
3. Good health
03 medical and health sciences
Genes, ras
Multivariate Analysis
Mutation
Humans
Female
Colorectal Neoplasms
Aged
Follow-Up Studies
Proportional Hazards Models
DOI:
10.1200/jco.2001.19.2.299
Publication Date:
2017-02-24T07:36:55Z
AUTHORS (9)
ABSTRACT
PURPOSE: Mutations in the K-ras gene are frequent in human cancer. ras activation in primary cells results in a cellular senescence phenotype that is precluded by inactivation of p16. At the clinical level, this may imply a differential behavior for tumors with alternative or cooperative activation of K-ras function and impairment of p16 pathways. PATIENTS AND METHODS: We have determined the presence of mutations in the K-ras gene and the methylation status of p16 promoter in a series of 119 prospectively collected colorectal carcinomas. p53 mutations and p14 alternative reading frame methylation status were also assessed. Associations with survival were investigated. RESULTS: K-ras mutations were present in 44 (38%) of 115 cases, and p16 methylation was present in 42 (37%) of 113 cases. p53 mutations were detected in 50% (56 of 115) and p14 methylation in 29% (32 of 112) of cases. K-ras and p16 alterations were independent genetic events. Presence of K-ras or p16 genetic alterations (analyzed independently) was associated with shorter survival, although differences were not statistically significant. Cox analysis of the two variables combined showed a diminished survival as the results of an interaction between p16 and K-ras. Alternative alteration of K-ras and p16 genes was an independent prognostic factor in human colorectal cancer in univariate and multivariate analysis. Differences were maintained when cases undergoing radical surgery and without distant metastases were considered. CONCLUSION: These results suggest that the combined K-ras and p16 analyses may be of prognostic use in human colorectal cancer.
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