The Role of K-ras Mutations in Pancreatic Neuroendocrine Tumors
K Gilliland, HJ Dong, S Hochwald, C Liu. University of Florida, Gainesville, Fl
Background: Mutations in K-ras appear to be early events in the progression of tumors in colorectal, pancreatic, and lung primary sites. K-ras mutations are important in the signaling pathway, downstream from the epidermal growth factor receptor (EGFR), and are usually due to a single base pair substitution. Mutations in codons 12 and 13 of the K-ras gene have been demonstrated in pancreatic and colonic adenocarcinomas with a reported incidence varying between 35-88%. However, K-ras mutations have not been studied extensively in pancreatic neuroendocrine tumors, particularly in a large cohort of cases, due to their relative rarity. The goal of this study is to determine the K-ras status in pancreatic neuroendocrine tumors.
Design: We examined 52 cases of pancreatic neuroendocrine tumors from the pathology files of our institution for the presence of K-ras mutations. Based on WHO criteria, the tumors were classified into 33 cases of well differentiated tumors, of which 12 were benign and 21 were uncertain behavior categories, and 19 cases of well differentiated endocrine carcinoma. DNA was extracted from formalin-fixed paraffin-embedded tissue, followed by PCR amplification of the K-ras gene. Sequencing of the K-ras gene product was performed using pyrosequencing at codons 12 and 13.
Results: No mutations were detected in codons 12 and 13 in all of the 52 cases of pancreatic neuroendocrine tumors. No sequence alterations were detected in well-differentiated (benign) pancreatic tumors, as well as uncertain metastatic potential and (malignant) pancreatic neuroendocrine carcinomas.
Conclusions: This study is the first to examine the role of K-ras mutations in pancreatic neuroendocrine tumors in a large cohort with pyrosequencing methods. Our findings suggest that mutations in codons 12 and 13 of the K-ras gene are not involved in the pathogenesis of pancreatic neuroendocrine tumors. This study indicates that the K-ras pathway may not be involved in pancreatic neuroendocrine tumors. Considering that the majority of pancreatic adenocarcinomas have K-ras mutations, K-ras sequencing analysis is valuable for differentiation of adenocarcinomas from neuroendocrine carcinomas in some cases.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 219, Tuesday Afternoon