Department of Molecular Diagnostics, PAMM Laboratory for Pathology; Fontys University of Applied Science.
Department of Molecular Diagnostics, PAMM Laboratory for Pathology.
Ann Oncol. 2010 Dec;21(12):2396-2402. doi: 10.1093/annonc/mdq258. Epub 2010 May 25.
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.
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.
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).
The V600E BRAF mutation confers a worse prognosis to stage II and stage III colon cancer patients independently of disease stage and therapy.
结直肠癌需要分子标志物来进行更准确的分类和个体化治疗。我们确定 BRAF 突变、微卫星不稳定性（MSI）和 KRAS 突变对 II 期和 III 期结肠癌的临床结局的影响。
仅接受手术治疗的 II 期结肠癌患者（n = 106）和接受 5-氟尿嘧啶化疗辅助治疗的 258 例 III 期患者均纳入研究。检测 KRAS 密码子 12 和 13、V600E BRAF 突变和 MSI 状态。
与 III 期相比，II 期患者更常为老年（P < 0.001）、右半结肠（P = 0.018）、分化更好（P = 0.003）和 MSI 肿瘤（P < 0.001）。在两组中，BRAF 突变与 MSI（P = 0.001）和 BRAF 突变与右半结肠肿瘤（P = 0.001）之间均存在正相关。BRAF 和 KRAS 突变是相互排斥的。在 II 期和 III 期合并数据的多变量生存分析中，BRAF 突变是总生存（OS）和癌症特异性生存的独立预后因素[风险比（HR）为 0.45，95%置信区间（CI）为 0.25-0.8 用于 OS 和 HR = 0.47，95%CI 为 0.22-0.99]。KRAS 突变导致无病生存（DFS）较差（HR = 0.6，95%CI 0.38-0.97）。
V600E BRAF 突变独立于疾病分期和治疗，为 II 期和 III 期结肠癌患者带来更差的预后。
