KRAS Mutation is a Local Tumour Event and Not a Field Change in Pancreatobiliary Tumours

Background: KRAS mutation (KRM) is the earliest, most common mutation in pancreatic cancer. Accurate assessment of tumour KRM status in pancreatobiiary tumours is relevant in an era of targeted molecular therapies.
Aim: To assess KRM in tumour and non-tumourous margin tissue in patients undergoing a pancreatic resection.
Study Design: Original research, retrospective review of prospectively collected specimens.
Place and Duration of Study: Patients who had undergone pancreaticoduodenectomy and distal pancreatic resection at the Royal Adelaide Hospital from 2011-2012 were consented for the study.
Methods: Patient demographics, background history and tumour details were collated. Tumour tissue and margin areas were macrodissected from FFPE tissue sections following identification by a pathologist. DNA was prepared from the tissue using the QIAamp FFPE Tissue kit (Qiagen GmbH, Hilden Germany). KRM at codons 12 and 13 was assessed using SNaPShot TM (Applied Biosystems, Warrington UK) in tumour tissue and non-tumourous margin tissue.
Fourteen patients were included in the study. The median age of the patients in the study was 68 (range 57-86) years. The M : F ratio was 8 : 6.
Results: Twelve patients had adenocarcinomas (5 pancreatic; 4 ampullary, 3 biliary) and two had benign mucinous tumours. Six patients with adenocarcinomas had KRM (5@codon 12 and 1@codon 13). Margin tissue was negative for KRM in all the tested patients (p<0.016 Fisher) particularly, in those with tumour KRM.
Tumours with KRM were associated with larger tumours 30(22-65) mm vs 20(15-35) mm [median(range)](p = .045 – MW-U). Nodal disease occurred in 6/6 with KRM vs 2/6 without KRM (p = .61 – Fisher).
Conclusions: KRM is a local tumour event and not a field change. This suggests that testing for KRM should be reliant on tumour tissue and not surrounding normal margin tissue. KRM was associated with larger malignant tumours and a trend towards nodal disease.