Pancreas · 2012
Frequencies and prognostic role of KRAS and BRAF mutations in patients with localized pancreatic and ampullary adenocarcinomas.
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Schultz Nicolai Aagaard, Roslind Anne, Christensen Ib J, Horn Thomas, Høgdall Estrid, Pedersen Lisbeth N, Kruhøffer Mogens, Burcharth Flemming, Wøjdemann Morten, Johansen Julia S
Аннотация
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.
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.
Предметные рубрики MeSH
AdenocarcinomaAdultAgedAged, 80 and overAmpulla of VaterCarcinoma, Pancreatic DuctalFemaleGene FrequencyGenotypeHumansKaplan-Meier EstimateMaleMiddle AgedMultivariate AnalysisMutationNeoplasm StagingPancreatic NeoplasmsPrognosisProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)Smokingras Proteins