Characterization of KRAS Mutation in Acinar and Langerhans Islet Cells of Patients With Pancreatic Ductal Adenocarcinoma

Abstract

KRAS mutations are frequent in pancreatic ductal adenocarcinoma, chronic pancreatitis, and mucinous neoplasms. In animal studies, KRAS mutations in acinar and Langerhans islets are associated with pancreatic intraepithelial neoplasia. Clinically, KRAS mutation is sometimes requested on cytology/biopsy specimens and negative results are helpful to rule out pancreatic ductal adenocarcinoma. This study set out to further elucidate these issues. Surgical specimens with pancreatic ductal adenocarcinoma, premalignant lesions, and chronic pancreatitis were reviewed. Tissue microdissections on 53 such areas of 21 cases were performed followed by polymerase chain reaction and pyrosequencing. KRAS codon 12 mutations were detected in 100% pancreatic ductal adenocarcinomas. No KRAS codon 12 and 13 mutations were detected in benign acinar and Langerhans islets that lie adjacent to or away from the tumor. Variable mutation frequencies were seen in premalignant lesions. The results support such clinical practice that negative KRAS mutation helps rule out pancreatic ductal adenocarcinomas on small cytology/biopsy specimens. Negative KRAS mutations, however, cannot rule out pancreatic premalignant lesions. Additionally, the results that benign pancreas are negative for KRAS mutations complement the findings of other relevant study that KRAS mutation-associated premalignant lesions do not appear to arise from acinar cells or Langerhans islets.