Cyst fluid interleukin-1beta (IL1beta) levels predict the risk of carcinoma in intraductal papillary mucinous neoplasms of the pancreas.

Maker, A.V., Katabi, N., Qin, L.X., Klimstra, D.S., Schattner, M., Brennan, M.F., Jarnagin, W.R., Allen, P.J.
Journal   Clin Cancer Res.
Species  
Analytes Measured   IL-10 , IL-12 Total , IL-13 , IL-2 , IL-4 , IL-5 , IL-8
Matrix Tested   Cyst fluid
Year   2011
Volume   17
Page Numbers   1502-8
Application   Cytokines and Chemokines
Abstract
PURPOSE: Biomarkers for high-grade dysplasia in patients with radiographically identified intraductal papillary mucinous neoplasms (IPMN) have not been described. We hypothesized that dysplasia in IPMN invokes an immunogenic/proinflammatory microenvironment that can be identified by cyst fluid cytokine levels.

EXPERIMENTAL DESIGN: Pancreatic cyst fluid aspirates were collected at resection (2005-2009). Samples were grouped into low-risk [low-grade (n = 6) or moderate dysplasia (n = 15)] and high-risk groups [high-grade dysplasia (n = 13) or carcinoma (n = 6)]. Cytokine expression was determined using a multiplex sandwich immunoassay. Differences in cytokine expression were evaluated using the 2-sample t test. Sample classification was performed using a logistic regression adjusting for sample covariates.

RESULTS: IL5 and IL8 concentrations were higher in the cyst fluid from patients in the high-risk group than the low-risk group. Interleukin (IL)-1β concentrations were also higher in the cyst fluid from patients with high-grade dysplasia or cancer (n = 19) than those with low- or moderate-grade dysplasia (n = 21, 539 ± 255 pg/mL vs. 0.2 ± 0.1 pg/mL; P < 0.0001). IL1β remained a significant predictor of high-risk cysts after multivariate analysis. There was no significant difference in levels of IL2, IL4, IL10, IL12, IL13, TNF-α, or IFN-γ between the groups. That IL1β levels identified cysts at a high risk of malignancy was confirmed in an independent validation set.

CONCLUSIONS: Cyst fluid levels of IL1β can differentiate low- from high-risk IPMN. This study introduces IL1β as a potential biomarker for validation in larger clinical studies.

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