Pancreatic cyst fluid and serum mucin levels predict dysplasia in intraductal papillary mucinous neoplasms of the pancreas.

Abstract

There are no reliable markers of dysplasia in patients with incidentally discovered intraductal papillary mucinous neoplasms of the pancreas (IPMN). IPMN dysplasia may be associated with mucin protein (MUC) expression and histopathologic subtype. We hypothesize that MUC expression in cyst fluid and serum can identify lesions with high risk of malignancy. Cyst fluid and serum were collected from 40 patients during pancreatectomy for IPMN between 2005 and 2009. Samples were grouped into low-risk (low-grade or moderate dysplasia, n = 21) and high-risk groups (high-grade dysplasia or carcinoma, n = 19). Mucin expression (MUC1, MUC2, MUC4, and MUC5AC) was assessed utilizing enzyme-linked immunosorbent assays. MUC2 and MUC4 cyst fluid concentrations were elevated in high-risk versus low-risk groups (10 ± 3.0 ng/ml vs. 4.4 ± 1.2 ng/ml, p = 0.03; 20.6 ± 10.6 ng/ml vs. 4.5 ± 1.4 ng/ml, p = 0.03, respectively). Corresponding serum samples revealed higher levels of MUC5AC in high-risk compared with low-risk patients (19.9 ± 9.3 ng/ml vs. 2.2 ± 1.1 ng/ml, p = 0.04). Histopathologic subtype was significantly associated with grade of dysplasia, and the intestinal subtype displayed increased MUC2 cyst fluid concentrations (13.8 ± 6.5 ng/ml vs. 4.1 ± 0.9 ng/ml, p = 0.02). In this study, high-risk IPMN showed elevated cyst fluid concentrations of MUC2 and MUC4, and increased serum levels of MUC5AC. High-risk IPMN also displayed a distinct mucin expression profile in specific histologic subtypes. These data, if validated, may allow surgeons to more appropriately select patients for operative resection.