K-ras Mutations Correlate with Atypical Cytology and Elevated CEA Levels in Pancreatic Cystic Neoplasms

Abstract

Benign pancreatic cystic neoplasms are important precursors to pancreatic adenocarcinoma, and offer the opportunity to prevent cancer. Conversely, prevention only occurs with surgical resection associated with significant morbidity and mortality, while the natural history of small cystic neoplasms is a slow and uncertain progression to malignancy. Markers that predict progression to malignancy are needed. Cyst fluid DNA analysis including K-ras mutations may predict more aggressive natural history of pancreatic cystic neoplasms. Sixty patients with pancreatic cysts measuring less than 3cm without solid component or pancreatic ductal dilation underwent EUS with fine needle aspiration. Nine had surgical resection. Cyst fluid was tested for cytology, CEA levels, and DNA analysis including K-ras mutations, and eight loss of heterozygosity mutations. Mutations were correlated with findings of atypia and CEA levels. Cyst fluid K-ras mutation was found in 30% of patients. Patients with mutated K-ras were more likely to have atypia on cytology or pathology (39 vs. 14%) and higher CEA (median 591 vs. 42) compared to wild-type K-ras. K-ras mutants were more likely to have two or more loss of heterozygosity mutations. Loss of heterozygosity mutations did not correlate with atypia or CEA levels. Cyst fluid K-ras mutation correlates with other markers of aggressive cyst behavior. EUS with cyst DNA analysis may alter management of smaller pancreatic cysts when surgery might otherwise be deferred. Further studies of cyst fluid DNA and long-term outcomes are needed.