局部胰腺和壶腹腺癌患者 KRAS 和 BRAF 突变的频率和预后作用。
Frequencies and prognostic role of KRAS and BRAF mutations in patients with localized pancreatic and ampullary adenocarcinomas.
机构信息
Department of Surgical Gastroenterology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
出版信息
Pancreas. 2012 Jul;41(5):759-66. doi: 10.1097/MPA.0b013e31823cd9df.
OBJECTIVES
The frequencies and prognostic role of KRAS and BRAF mutations in patients operated on for pancreatic ductal adenocarcinomas (PDACs) and ampullary adenocarcinomas (A-ACs) are scantily studied.
METHODS
KRAS and BRAF mutations were analyzed in formalin-fixed, paraffin-embedded tumor samples from primarily chemotherapy-naive patients operated on with radical intentions for PDAC (n = 170) and A-AC (n = 107).
RESULTS
Eighty percent of PDAC patients had KRAS mutations (codon 12 mutations: 74%) and 67% with A-AC (codon 12 mutations: 54%). BRAF mutations were less common, 16% in PDAC and 12% in A-AC, and no V600E mutations were found. Fourteen percent with PDAC and 7% with A-AC had mutations in both KRAS and BRAF. Multivariate analysis, including KRAS status, stage, and American Society of Anesthesiologists physical status classification system score, demonstrated that KRAS mutations in patients with A-AC were associated with short recurrence-free survival (RFS) (hazard ratio, 2.45; 95% confidence interval, 1.19-5.06; P = 0.015) and overall survival (OS) (1.93, 95% 1.12-3.31; P = 0.018). KRAS mutations in patients with PDAC were not associated with RFS and OS. BRAF mutations were not associated with RFS and OS.
CONCLUSIONS
KRAS mutations frequencies were high in PDAC and A-AC. KRAS mutations were associated with poor prognosis in patients with A-AC, but not in patients with PDAC.
目的
在接受根治性手术治疗的胰腺导管腺癌(PDAC)和壶腹腺癌(A-AC)患者中,KRAS 和 BRAF 突变的频率及其预后作用研究甚少。
方法
对 170 例初治接受根治性手术的 PDAC 患者和 107 例初治接受根治性手术的 A-AC 患者的福尔马林固定石蜡包埋肿瘤样本进行 KRAS 和 BRAF 突变分析。
结果
80%的 PDAC 患者存在 KRAS 突变(密码子 12 突变:74%),67%的 A-AC 患者存在 KRAS 突变(密码子 12 突变:54%)。BRAF 突变较少见,PDAC 患者为 16%,A-AC 患者为 12%,未发现 V600E 突变。14%的 PDAC 患者和 7%的 A-AC 患者同时存在 KRAS 和 BRAF 突变。包括 KRAS 状态、分期和美国麻醉医师协会身体状况分类系统评分在内的多变量分析表明,A-AC 患者的 KRAS 突变与无复发生存率(RFS)(风险比,2.45;95%置信区间,1.19-5.06;P = 0.015)和总生存(OS)(1.93,95%置信区间,1.12-3.31;P = 0.018)缩短相关。PDAC 患者的 KRAS 突变与 RFS 和 OS 无关。BRAF 突变与 RFS 和 OS 无关。
结论
PDAC 和 A-AC 中 KRAS 突变频率较高。KRAS 突变与 A-AC 患者的预后不良相关,但与 PDAC 患者的预后无关。