Increasing use of high resolution computerized tomography and magnetic resonance imaging in clinical practice has resulted in detection of a growing number of pancreatic cysts 1
. As a result, clinicians are frequently asked to determine the biological nature of these cystic lesions and to make treatment recommendations accordingly. However, there are currently no diagnostic indicators that are consistently reliable, obtainable, and conclusive for diagnosing and risk-stratifying pancreatic cysts. The sensitivity of pancreatic cyst fluid cytology has been reported as only 27–64%. Several studies have suggested that a variety of tumor markers (e.g., CEA (carcinoembryonic antigen CEACAM5, a carcinoembryonic antigen-related cell adhesion molecule) 2
, CA 19-9 (carbohydrate antigen 19-9), CA 15-3 (cancer antigen MUC1, mucin 1) may distinguish mucinous from non-mucinous cystic lesions, and also may predict whether a cyst harbors areas of malignant transformation 3–5
, but no marker by itself is sufficiently reliable.
The biologic nature and histopathologic features of pancreatic cysts are varied 3, 6
. Ten to twenty percent of pancreatic cysts are neoplastic, including neoplasms which grow as cystic structures (i.e., primary cystic neoplasms of the pancreas), and solid neoplasms that have undergone cystic degeneration. Serous cystadenomas (microcystic adenomas) account for approximately 32–39% of the primary cystic neoplasms and have very low malignant potential. Mucinous cystic neoplasms, which includes mucinous cystadenomas (MCAs) and intraductal papillary mucinous neoplasms (IPMNs), are a subgroup of primary cystic neoplasms that have malignant potential 7, 8
, accounting for approximately 10–45% and 21–33% of primary cystic neoplasms, respectively 6, 9–11
. Two subtypes of IPMN have been described 1, 12
, a main duct variant and a branch duct variant; the latter may have a more indolent course. There are other less common forms of primary cystic neoplasms of the pancreas, such as solid pseudopapillary tumors.
In the absence of reliable methods of quantifying the malignant potential of a suspected pre-malignant cystic neoplasm of the pancreas, if existing clinical parameters suggest the presence of one such lesion in a person that is otherwise an acceptable surgical risk, partial or total pancreatomy may be recommended but can result in significant morbidity and mortality 13
. Alternatively, a conservative "watch-and-wait” approach (i.e., serial imaging over time) is advocated for some patients, but this strategy may be suboptimal due to incremental costs accrued during surveillance, and the possibility that malignant transformation may occur between surveillance time points.
Our primary goal was to define a reliable and reproducible technique for analyzing pancreatic cyst fluids with proteomics. Our secondary goals were to ascertain whether mass spectrometry proteomics can be performed with much smaller volumes than is required for the clinical assays that are currently used to study pancreatic cyst fluid, and also to provide an assessment of whether proteomics can define potentially useful diagnostic and/or risk-stratifying pancreatic cyst biomarkers or biomarker profiles. We performed a meticulous proteomic study consistent with the guide line described in the recent review article in Pancreas 14