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

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Fig. 1

Gastric subtype correlated with MUC expression. Expression of MUCs 2, 4, and 5AC were significantly decreased in gastric (n = 23) compared with nongastric cysts (n = 17). * p < 0.05

Fig. 2

Intestinal subtype correlated with MUC expression. Expression of MUC2 and MUC4 were increased in intestinal compared with nonintestinal cysts (p = 0.03* and 0.054, respectively)

Fig. 3

MUC2 and MUC4 expression by degree of cyst dysplasia. Levels of MUC2 and MUC4 were significantly elevated in high-risk cysts compared with low-risk cysts. Mod moderate dysplasia, HGD high-grade dysplasia, Ca invasive cancer

Fig. 4

Serum levels of MUC5AC. Serum levels of MUC5AC were elevated in patients with high-risk cysts compared with low-risk cysts (17.9 ± 9.3 vs. 2.2 ± 1.1 ng/ml, p = 0.025) in a small number of patients (high risk, n = 12, low risk, n = 14). Data points from the three serum samples of patients with invasive IPMN are denoted by crosses