The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients.
BACKGROUND
Molecular markers in colon cancer are needed for a more accurate classification and personalized treatment. We determined the effects on clinical outcome of the BRAF mutation, microsatellite instability (MSI) and KRAS mutations in stage II and stage III colon carcinoma.


METHODS
Stage II colon carcinoma patients (n = 106) treated with surgery only and 258 stage III patients all adjuvantly treated with 5-fluorouracil chemotherapy were included. KRAS mutations in codons 12 and 13, V600E BRAF mutation and MSI status were determined.


RESULTS
Older patients (P < 0.001), right-sided (P = 0.018), better differentiated (P = 0.003) and MSI tumors (P < 0.001) were significantly more frequent in stage II than stage III. In both groups, there was a positive association between mutated BRAF and MSI (P = 0.001) and BRAF mutation and right-sided tumors (P = 0.001). Mutations in BRAF and KRAS were mutually exclusive. In a multivariate survival analysis with pooled stage II and stage III data, BRAF mutation was an independent prognostic factor for overall survival (OS) and cancer-specific survival [hazards ratio (HR) = 0.45, 95% confidence interval (CI) 0.25-0.8 for OS and HR = 0.47, 95% CI 0.22-0.99]. KRAS mutation conferred a poorer disease-free survival (HR = 0.6, 95% CI 0.38-0.97).


CONCLUSIONS
The V600E BRAF mutation confers a worse prognosis to stage II and stage III colon cancer patients independently of disease stage and therapy.
Fariña-Sarasqueta
A
A
Department of Molecular Diagnostics, PAMM Laboratory for Pathology; Fontys University of Applied Science.
van Lijnschoten
G
G
Department of Molecular Diagnostics, PAMM Laboratory for Pathology.
Moerland
E
E
Department of Molecular Diagnostics, PAMM Laboratory for Pathology.
Creemers
G-J
GJ
Department of Internal Medicine and Oncology, Catharina Hospital Eindhoven.
Lemmens
V E P P
VEPP
Department of Research, Comprehensive Cancer Centre South.
Rutten
H J T
HJT
Department of Surgical Oncology.
van den Brule
A J C
AJC
Department of Molecular Diagnostics, PAMM Laboratory for Pathology; Department of Molecular Diagnostics, Catharina Hospital Eindhoven, Eindhoven, The Netherlands. Electronic address: a.van.den.brule@pamm.nl.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000502:physiology; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D011905:Genes, ras; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D020125:Mutation, Missense / Q000502:physiology; D009367:Neoplasm Staging; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016019:Survival Analysis; D014633:Valine / Q000235:genetics
D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine