KRAS mutations correlates with P53 status in colorectal carcinomas

Natalia Rodón1, Ruth Román1, Montse Verdú1,3, Miquel Calvo4, Beatriz García-Peláez1, Marta González1, Carme Pubill3 y Xavier Puig1,2,3.

1BIOPAT. Biopatologia Molecular, SL, Grup Assistència; 2Hospital de Barcelona-SCIAS, Grup Assistència; 3Histopat Laboratoris; 4Departament d’Estadística, Universitat de Barcelona. Barcelona


KRAS mutations, present in approximately 30-50% of colorectal carcinomas (CRC) has been recently associated with lack of response to anti-EGFR therapy, poor prognosis and high mitotic activity. Nevertheless, its relation to other histopathological and molecular parameters has not been well established.

Our first approach was to determine correlations between KRAS status and histopathologic and molecular findings in an univariate analysis using a retrospective series of 337 CRC cases.


25 histopathological features were evaluated, including Ki67 and p53 immunoexpression. Mutational analysis of P53 and BRAF was carried out by direct sequencing. Statistical analysis was performed by Kruskal-Wallis and Fisher’s exact tests.


KRAS mutations were identified in 144 out of 337 cases (42.7%). BRAF V600E was found in 32 cases out of 318 (10.1%), 31 of them in KRAS wild-type group (p<0.001). 72 cases out of 144 with KRAS mutated contained P53 mutations (50%). In the KRAS wild-type group, 133 cases (70%) harbour P53 mutations (p<0.001). The p53 immunoexpression was also significantly higher in the KRAS wild-type group (p= 0.009). Significant differences were also observed between KRAS mutations and mucinous (p=0.001) and solid tumoral patterns (p=0.010).


KRAS (42.7%) and BRAF V600E mutations were found to be mutually exclusive in agreement with published data. The P53 mutated status is significantly associated with KRAS wild-type (p<0.001) but is also frequent in the KRAS mutated group, suggesting P53 inactivation arises through independent pathways. A multivariate analysis would be required to further analyse these correlations.

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Virchows Archiv 2009; 455 (suppl 1): S392.