A Fariña-Sarasqueta1, G van Lijnschoten2, E Moerland2, G-J Creemers3, V E P P Lemmens4, H J T Rutten5, A J C van den Brule6. 1. Department of Molecular Diagnostics, PAMM Laboratory for Pathology; Fontys University of Applied Science. 2. Department of Molecular Diagnostics, PAMM Laboratory for Pathology. 3. Department of Internal Medicine and Oncology, Catharina Hospital Eindhoven. 4. Department of Research, Comprehensive Cancer Centre South. 5. Department of Surgical Oncology. 6. 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.
Abstract
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. PATIENTS AND 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.
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. PATIENTS AND METHODS: Stage II colon carcinomapatients (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, V600EBRAF 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 V600EBRAF mutation confers a worse prognosis to stage II and stage III colon cancerpatients independently of disease stage and therapy.
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