Frequencies and prognostic role of KRAS and BRAF mutations in patients with localized pancreatic and ampullary adenocarcinomas.
OBJECTIVE
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.
Department of Surgical Gastroenterology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. nicolai-schultz@dadlnet.dk
Nicolai Aagaard
NA
Schultz
Anne
A
Roslind
Ib J
IJ
Christensen
Thomas
T
Horn
Estrid
E
Høgdall
Lisbeth N
LN
Pedersen
Mogens
M
Kruhøffer
Flemming
F
Burcharth
Morten
M
Wøjdemann
Julia S
JS
Johansen
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012907:Smoking; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins