Frequencies and Prognostic Role of KRAS and BRAF Mutations in Patients With Localized Pancreatic and Ampullary Adenocarcinomas : Pancreas

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Original Articles

Frequencies and Prognostic Role of KRAS and BRAF Mutations in Patients With Localized Pancreatic and Ampullary Adenocarcinomas

Schultz, Nicolai Aagaard MD*†; Roslind, Anne MD, PhD; Christensen, Ib J. MS§; Horn, Thomas DMSc, MD; Høgdall, Estrid PhD; Pedersen, Lisbeth N. MD, PhD; Kruhøffer, Mogens PhD; Burcharth, Flemming MD, DMSc*; Wøjdemann, Morten MD, DMSc*; Johansen, Julia S. DMSc, MD#**

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Pancreas 41(5):p 759-766, July 2012. | DOI: 10.1097/MPA.0b013e31823cd9df

Abstract

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.

© 2012 Lippincott Williams & Wilkins, Inc.

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