Mo1410 Mutational Analysis of Pancreatic Cystic Tumors: A Series Based on Surgical Pathology

Mo1410 Mutational Analysis of Pancreatic Cystic Tumors: A Series Based on Surgical Pathology Megan D. Winner, Amrita Sethi, John M. Poneros, Peter D. Stevens, John D. Allendorf, John A. Chabot, Tamas A. Gonda Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY; Division of Digestive and Liver Diseases, Columbia University, New York, NY Introduction: The accurate pre-operative characterization of pancreatic cystic neoplasms and stratification of those most likely to harbor invasive cancer is one of the greater diagnostic challenges in the field. Analysis of cyst fluid DNA for the presence of K-ras mutations and loss of heterozygosity (LOH) may improve the assessment of risk associated with pancreatic cystic neoplasms. We assessed the accuracy of these molecular markers in distinguishing mucinous cysts and invasive cancer in a large cohort of patients who underwent surgical resection. Methods: We retrospectively reviewed patients who underwent surgical resection of a pancreatic cystic lesion at our institution and selected those who had endoscopic ultrasound/fine needle aspiration (EUS/FNA) and cyst fluid analysis for the presence of K-ras mutation and loss of heteozygosity (LOH). Molecular analysis was performed by RedPath IP (Pittsburgh, PA). Neoplasms pathologically characterized as high-grade, carcinoma in situ, and invasive cancer were considered malignant. Fisher’s exact test was used to analyze categorical variables and kappa values were generated for inter-test agreement. Results: Between January 1997 and September 2010, 192 patients had EUS/FNA with analysis of cyst fluid molecular markers and 278 have undergone surgical resection of a cystic lesion of the pancreas. Thirty-nine of these had preoperative assessment of molecular markers. Final pathology included 16 IPMNs, 4 IPMCs, 8 MCNs, 4 NETs, 3 serous cystadenomas, and 2 ductal adenocarcinomas. Sixty-seven percent of the lesions were mucinous and 20% were malignant. Forty-two percent of cysts harbored a K-ras mutation. Fortyeight percent had at least one LOH and 34% had more than one LOH. Twentysix patients had sufficient fluid for carcinoembryonic antigen (CEA) analysis and cytology was adequate in 25. The sensitivity and specificity of a K-ras mutation and LOH for mucinous pathology was low; however, their combined sensitivity was 79%. Cyst fluid CEA 192 was almost as sensitive (73.7%) and more specific (71.4%), but agreement between CEA 192 and K-ras/LOH was poor (kappa 0.138). The sensitivity of both the K-ras mutation and cytopathology for malignancy was low; however, LOH had a notably higher sensitivity for the diagnosis of malignancy and was significantly associated with the presence of malignancy (p 0.01). The combination of a K-ras mutation and/or LOH did not increase the sensitivity, but lowered both the specificity and the negative predictive value. Conclusions: In this series we found the presence of a K-ras mutation or LOH to have limited value in distinguishing mucinous from nonmucinous lesions. Fluid CEA, although limited by sample size in this study, had better accuracy. In our series, LOH but not a K-ras mutation was significantly associated with the presence of malignancy.