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

Authors: Maker, AV  Katabi, N  Qin, LX  Klimstra, DS  Schattner, M  Brennan, MF  Jarnagin, WR  Allen, PJ 
Citation: Maker AV, etal., Clin Cancer Res. 2011 Mar 15;17(6):1502-8. doi: 10.1158/1078-0432.CCR-10-1561. Epub 2011 Jan 25.
Pubmed: (View Article at PubMed) PMID:21266527
DOI: Full-text: DOI:10.1158/1078-0432.CCR-10-1561

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)-1beta 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). IL1beta 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-alpha, or IFN-gamma between the groups. That IL1beta levels identified cysts at a high risk of malignancy was confirmed in an independent validation set. CONCLUSIONS: Cyst fluid levels of IL1beta can differentiate low- from high-risk IPMN. This study introduces IL1beta as a potential biomarker for validation in larger clinical studies.

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CRRD Object Information
CRRD ID: 7794719
Created: 2014-01-08
Species: All species
Last Modified: 2014-01-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.