KRAS-/BRAF-status in stage III colorectal cancer – correlation with morphological parameters and prognostic impact
D.E. Aust1, M.P. Lutz2, M. Mauer3, Ivan Popov4, C.H. Köhne5, G.B. Baretton1
1Institut für Pathologie, Universitätsklinikum Carl Gustav Carus, Dresden
2 Caritasklinik St. Theresia, Saarbrücken;
3 EORTC Headquarters, Brüssel, Belgien;
4 Institute for Oncology and Radiology, Department for Medical Oncology, Serbien;
5 Klinikum Oldenburg, Abt. Onkologie und Hämatologie
Aims: KRAS and possibly BRAF mutations are negative predictors for anti-EGFR therapy in colorectal cancer (CRC). The prognostic impact of these mutations in CRC is less clear. This study aimed to assessthe correlation of KRAS-/BRAF-status with morphological characteristics and its prognostic impact for long term outcome in UICC-stage III CRC.
Methods: FFPE material was collected from 493 CRC treated with adjuvant 5-FU monotherapy in the PETACC2 trial. KRAS mutations were detected by direct sequencing (ABI Prism 310), BRAF mutations by pyrosequencing (Pyromark Q24). Statistical analysis was done using Fisher exact test and Kaplan Meier survival analyses at a level of significance of 0.05.
Results: While KRAS mutations did not correlate with any pathological parameters, BRAF mutations were significantly associated with mucinous histology, higher pT-stage, poor differentiation and location in the right-sided colon. Neither KRAS- nor BRAF-status showed any impact on disease-free and overall survival in univariate analyses.
Conclusions: KRAS-/BRAF-status does not have any prognostic impact in CRC treated with 5FU-monotherapy. While BRAF mutations are associated with certain morphological characteristics, KRAS mutations are not.