Cyst fluid interleukin-1β (IL1β) levels predict the risk of carcinoma in intraductal papillary mucinous neoplasms of the pancreas Journal Article


Authors: Maker, A. V.; Katabi, N.; Qin, L. X.; Klimstra, D. S.; Schattner, M.; Brennan, M. F.; Jarnagin, W. R.; Allen, P. J.
Article Title: Cyst fluid interleukin-1β (IL1β) 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 [highgrade 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)-1b 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 IL1b as a potential biomarker for validation in larger clinical studies. ©2011 AACR.
Keywords: clinical article; controlled study; cancer risk; nonhuman; interleukin 2; carcinoembryonic antigen; interleukin 10; interleukin 13; interleukin 1beta; interleukin 4; interleukin 5; interleukin 8; cystadenoma; intraductal papillary mucinous tumor; pancreas cyst; cyst fluid; animal model; pancreas carcinoma; tumor necrosis factor alpha; gamma interferon; aspiration biopsy; interleukin 12; predictive value; dysplasia; receiver operating characteristic
Journal Title: Clinical Cancer Research
Volume: 17
Issue: 6
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2011-03-15
Start Page: 1502
End Page: 1508
Language: English
DOI: 10.1158/1078-0432.ccr-10-1561
PROVIDER: scopus
PUBMED: 21266527
PMCID: PMC3065716
DOI/URL:
Notes: --- - "Export Date: 23 June 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Murray F Brennan
    789 Brennan
  2. Nora Katabi
    161 Katabi
  3. Li-Xuan Qin
    116 Qin
  4. David S Klimstra
    858 Klimstra
  5. Peter Allen
    446 Allen
  6. William R Jarnagin
    599 Jarnagin
  7. Mark Schattner
    104 Schattner