In addition , only 5 of the 51 measured proteins were differentially expressed (IL-2, P= 0. 002; IL-1b, P= 0. 006; IFN gamma, P= 0. 02; CA724, P= 0. 03; and MPO, P= 0. 03) between excluded and included IPMN patients. was identified between SCA and IPMN (34/51 proteins, 67%) and between SCA and MCN (13/51 proteins, 25%). The majority of proteins were down-regulated in IPMN and MCN compared with SCA. The only proteins significantly overexpressed in the cyst fluid of patients with mucinous cysts were CEA (median FI: IPMN 11. 4, MCN 13. 0, SCA 5. 3; P < 0. 001, IPMN vs . SCA) and CA72. 4 (median FI: IPMN 10. 4, MCN PROCR 10. 5, SCA 9. 9; P= 0. 003, IPMN vs . SCA). Unsupervised cluster analysis demonstrated distinct clustering of SCA and IPMN with some cross-over between MCN. Supervised sample classification with 14 proteins had an overall accuracy rate of 92% between SCA and IPMN. == Conclusions == In this study differential cyst fluid protein expression was noticed between SCA and IPMN for the majority of proteins assessed and multimarker sample classification accurately discriminated between SCA and IPMN in 92% of patients. Over the past decade the increased availability of high quality cross-sectional imaging has resulted in more patients diagnosed with cystic lesions of the pancreas. 1, 2At Kobe2602 Massachusetts General Hospital, 16% of pancreatic resections performed in 1991 were intended for cystic lesions of the pancreas, and in 1998 the percentage of resections performed for pancreatic cysts had increased to 30%. 1This past 12 months at our institution (Memorial Sloan-Kettering Cancer Center [MSKCC, ] 2007), surgeons and gastroenterologists evaluated over 200 new patients with pancreatic cysts. A cystic lesion of the pancreas is a radiographic finding with a broad histologic differential. This histologic differential includes non-neoplastic pseudocysts, as well as benign, premalignant, and malignant neoplasms. Improved imaging techniques, as well as an improved understanding of the nature of these lesions, has made possible the distinction between non-neoplastic pseudocysts and cystic neoplasms in most of cases. 3Because of this, current research efforts have focused on developing techniques to differentiate between the most common neoplastic cysts. Currently, over 90% of patients undergoing resection for a cystic neoplasm of the pancreas will have the histologic diagnosis of a serous cystadenoma (SCA), intraductal papillary mucinous neoplasm (IPMN), or mucinous cystic neoplasm (MCN) with the majority of these being either SCA or IPMN. 4Preoperative determination of histologic subtype is critical, as SCAs are considered benign and generally do not require resection, whereas IPMNs and MCNs (mucinous cysts) are considered premalignant. Because current diagnostic tests are unable to reliably identify mucinous cysts, many institutions have recommended routine resection of pancreatic cysts. 5, 6This approach exposes asymptomatic patients with benign lesions to the risks of pancreatectomy intended for no identifiable benefit. The purpose of this study was to assess the diagnostic precision of proteomic profiling of pancreatic cyst fluid obtained from patients with Kobe2602 noninvasive and radiographically equivocal cysts. Differential protein expression was assessed in the cyst fluid from resected SCA, IPMN, and MCN. Sample classification and unsupervised cluster analyses were performed to assess the precision of this proteomic approach. Kobe2602 == METHODS == Patients undergoing resection for a cystic lesion of the pancreas at MSKCC were consented to the IRB approved tissue, serum, and cyst fluid protocol (MSKCC IRB 00032). Resected specimens were immediately transported to the MSKCC tumor procurement facility where cyst aspiration was performed by a surgeon, pathologist, or technician. Cyst fluid samples were aspirated with an 18 to 21 gauge needle, divided into 500L aliquots, and stored at 80C. The time between resection and freezing was recorded and only samples that had been frozen within 60 minutes of resection were used. None of the samples had undergone any freeze-thaw cycles before analysis. Histopathologic assessment of resected specimens was performed within the Department of Pathology (MSKCC). Results were reviewed at monthly multidisciplinary staging conferences and stored with the Department of Surgery pancreatic database. In this study only cyst fluid specimens from patients with SCA (n = 15), noninvasive IPMN (n = 32), or noninvasive MCN (n = 12) were used. Patients with invasive IPMN or isolated main duct IPMN were excluded as the radiographic findings in these patients are typically not equivocal and operative resection is routinely recommended. Multianalyte analysis (Luminex) of the cyst fluid was performed at the University of Pittsburgh Medical Center using an antibody microsphere array panel that has been designed and developed intended for pancreatic cancer. Commercially available and custom designed multiplex assays were used (Biosource International, Linco Research). The 54 unique proteins measured in this analysis are listed inTable 1 . == TABLE 1 . == Biomarkers Used in the Multianalyte Analysis of 59 Patients Resected With SCA, IPMN, or MCN Multianalyte analysis was performed according to.