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

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.

©2011 AACR.

Figures

Figure 1

Levels of interleukin-1b (IL1b), IL5, and IL8 were increased in high risk cysts (high grade dysplasia (HGD) or invasive cancer (Ca), n=19) compared to low risk cysts (low grade dysplasia (low) or moderate dysplasia (mod), n=21), *p

Figure 2

Receiver operating characteristic curve for IL1b shows an area under the curve of 0.92 (p