Cyst fluid interleukin-1beta (IL1beta) levels predict the risk of carcinoma in intraductal papillary mucinous neoplasms of the pancreas
Ajay V Maker, Nora Katabi, Li-Xuan Qin, David S Klimstra, Mark Schattner, Murray F Brennan, William R Jarnagin, Peter J Allen, Ajay V Maker, Nora Katabi, Li-Xuan Qin, David S Klimstra, Mark Schattner, Murray F Brennan, William R Jarnagin, Peter J Allen
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
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Figure 2
Receiver operating characteristic curve for…
Figure 2
Receiver operating characteristic curve for IL1b shows an area under the curve of…
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- Prostaglandin E2: A Pancreatic Fluid Biomarker of Intraductal Papillary Mucinous Neoplasm Dysplasia.Yip-Schneider MT, Carr RA, Wu H, Schmidt CM. Yip-Schneider MT, et al. J Am Coll Surg. 2017 Oct;225(4):481-487. doi: 10.1016/j.jamcollsurg.2017.07.521. Epub 2017 Jul 21. J Am Coll Surg. 2017. PMID: 28739154 Free PMC article.
- Pancreatic cyst fluid and serum mucin levels predict dysplasia in intraductal papillary mucinous neoplasms of the pancreas.Maker AV, Katabi N, Gonen M, DeMatteo RP, D'Angelica MI, Fong Y, Jarnagin WR, Brennan MF, Allen PJ. Maker AV, et al. Ann Surg Oncol. 2011 Jan;18(1):199-206. doi: 10.1245/s10434-010-1225-7. Epub 2010 Aug 18. Ann Surg Oncol. 2011. PMID: 20717734 Free PMC article.
- Cyst fluid biomarkers for intraductal papillary mucinous neoplasms of the pancreas: a critical review from the international expert meeting on pancreatic branch-duct-intraductal papillary mucinous neoplasms.Maker AV, Carrara S, Jamieson NB, Pelaez-Luna M, Lennon AM, Dal Molin M, Scarpa A, Frulloni L, Brugge WR. Maker AV, et al. J Am Coll Surg. 2015 Feb;220(2):243-53. doi: 10.1016/j.jamcollsurg.2014.11.001. Epub 2014 Nov 6. J Am Coll Surg. 2015. PMID: 25592469 Free PMC article. No abstract available.
- Intraductal papillary mucinous neoplasms.Sahora K, Fernández-del Castillo C. Sahora K, et al. Curr Opin Gastroenterol. 2015 Sep;31(5):424-9. doi: 10.1097/MOG.0000000000000198. Curr Opin Gastroenterol. 2015. PMID: 26125316 Review.
- Limitations and prospects in the management of IPMN: a retrospective, single-center observational study.Peisl S, Burckhardt O, Egger B. Peisl S, et al. BMC Surg. 2023 Jan 7;23(1):3. doi: 10.1186/s12893-023-01902-1. BMC Surg. 2023. PMID: 36611137 Free PMC article.
- The Landmark Series: Intraductal Papillary Mucinous Neoplasms of the Pancreas-From Prevalence to Early Cancer Detection.Pollini T, Wong P, Maker AV. Pollini T, et al. Ann Surg Oncol. 2023 Mar;30(3):1453-1462. doi: 10.1245/s10434-022-12870-w. Epub 2023 Jan 4. Ann Surg Oncol. 2023. PMID: 36600097 Free PMC article. Review.
- Early diagnosis of pancreatic cancer: What strategies to avoid a foretold catastrophe.Tonini V, Zanni M. Tonini V, et al. World J Gastroenterol. 2022 Aug 21;28(31):4235-4248. doi: 10.3748/wjg.v28.i31.4235. World J Gastroenterol. 2022. PMID: 36159004 Free PMC article. Review.
- The tumour immune microenvironment and microbiome of pancreatic intraductal papillary mucinous neoplasms.Pollini T, Adsay V, Capurso G, Dal Molin M, Esposito I, Hruban R, Luchini C, Maggino L, Matthaei H, Marchegiani G, Scarpa A, Wood LD, Bassi C, Salvia R, Mino-Kenudson M, Maker AV. Pollini T, et al. Lancet Gastroenterol Hepatol. 2022 Dec;7(12):1141-1150. doi: 10.1016/S2468-1253(22)00235-7. Epub 2022 Aug 31. Lancet Gastroenterol Hepatol. 2022. PMID: 36057265 Review.
- Circulating cytokines allow for identification of malignant intraductal papillary mucinous neoplasms of the pancreas.Pu N, Chen Q, Zhang J, Yin H, Wang D, Ji Y, Rao S, Kuang T, Xu X, Wu W, Lou W. Pu N, et al. Cancer Med. 2023 Feb;12(4):3919-3930. doi: 10.1002/cam4.5051. Epub 2022 Jul 24. Cancer Med. 2023. PMID: 35871313 Free PMC article.
- Research Support, N.I.H., Extramural
- Adenocarcinoma, Mucinous / metabolism*
- Biomarkers, Tumor
- Carcinoma / metabolism*
- Carcinoma, Pancreatic Ductal / metabolism*
- Cyst Fluid / metabolism*
- Cytokines / biosynthesis
- Female
- Humans
- Interleukin-1beta / metabolism*
- Interleukin-5 / biosynthesis
- Interleukin-8 / biosynthesis
- Male
- Pancreatic Neoplasms / metabolism*
- ROC Curve
- Biomarkers, Tumor
- Cytokines
- Interleukin-1beta
- Interleukin-5
- Interleukin-8
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- Other Literature Sources
- Medical
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Source: PubMed