Tumor-associated neutrophils and malignant progression in intraductal papillary mucinous neoplasms an opportunity for identification of high-risk disease Journal Article

   

Authors:	Sadot, E.; Basturk, O.; Klimstra, D. S.; Gönen, M.; Lokshin, A.; Do, R. K. G.; D'Angelica, M. I.; DeMatteo, R. P.; Peter Kingham, T; Jarnagin, W. R.; Allen, P. J.
Article Title:	Tumor-associated neutrophils and malignant progression in intraductal papillary mucinous neoplasms an opportunity for identification of high-risk disease
Abstract:	Objectives: To evaluate the association of tumor-associated neutrophils (TANs) with malignant progression in intraductal papillary mucinous neoplasms (IPMNs) and to study the cyst fluid from these lesions for biomarkers of the inflammation-carcinogenesis association. Background: There is a strong link between TANs and malignant progression. Inflammatory mediators released by these cells may be a measurable surrogate marker of this progression. Methods: We evaluated 78 resected IPMNs (2004-2013). Lesions were divided into the low-risk (low-and intermediate-grade dysplasia: n=48) and high-risk (high-grade dysplasia and invasive carcinoma: n=30) groups. TANs were assessed and categorized (negative, low, and high). A multiplexed assay was performed to evaluate 87 different cyst fluid proteins, including cyst fluid inflammatory markers (CFIMs), as possible surrogate markers for parenchymal inflammation. Results: Significant positive correlation between grade of dysplasia and TANs was found. High levels of TANs were identified in 2%, 33%, and 89% of the lesions when stratified by grade of dysplasia into low/intermediate-grade dysplasia, high-grade dysplasia, and invasive carcinoma, respectively (P<0.001). Higher grades of dysplasia were also found to have positive correlation with 29 of the measured proteins, of which 23 (79%) were CFIMs. Higher levels of TANs correlated with higher levels of 18 CFIMs, of which 16 (89%) were also found to be associated with higher grades of dysplasia. Conclusions: In this study, TANs were strongly associated with malignant progression in IPMNs. Measurement of CFIMs may be a surrogate marker for IPMN progression and allow for the identification of high-risk disease. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Keywords:	adult; human tissue; aged; major clinical study; histopathology; cancer growth; conference paper; disease marker; pancreas; biological marker; intraductal papillary mucinous tumor; cyst fluid; inflammation; high risk patient; carcinogenesis; neutrophil; malignant progression; neutrophils; invasive carcinoma; dysplasia; tumor microenvironment; intermediate risk patient; intraductal papillary mucinous neoplasms; low risk patient; human; male; female; priority journal; tumor associated neutrophil
Journal Title:	Annals of Surgery
Volume:	262
Issue:	6
ISSN:	0003-4932
Publisher:	Lippincott Williams & Wilkins
Date Published:	2015-12-01
Start Page:	1102
End Page:	1107
Language:	English
DOI:	10.1097/sla.0000000000001044
PROVIDER:	scopus
PMCID:	PMC4643387
PUBMED:	25563865
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84948709986&partnerID=40&md5=fb4fe123b0dd833443a356e9aa1840cb
Notes:	Export Date: 15 January 2016 -- Conference Paper -- Source: Scopus

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