Dataset Information

Tumor-associated Neutrophils and Malignant Progression in Intraductal Papillary Mucinous Neoplasms: An Opportunity for Identification of High-risk Disease.

ABSTRACT: 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.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.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.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?

SUBMITTER: Sadot E

PROVIDER: S-EPMC4643387 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Tumor-associated Neutrophils and Malignant Progression in Intraductal Papillary Mucinous Neoplasms: An Opportunity for Identification of High-risk Disease.

Sadot Eran E Basturk Olca O Klimstra David S DS Gönen Mithat M Lokshin Anna A Do Richard Kinh Gian RK D'Angelica Michael I MI DeMatteo Ronald P RP Kingham T Peter TP Jarnagin William R WR Allen Peter J PJ

Annals of surgery 20151201 6

<h4>Objectives</h4>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.<h4>Background</h4>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.<h4>Methods</h4>We evaluated 78 resected ...[more]

PMID: 25563865

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Project description:Purpose: The diagnosis of high grade intraductal papillary mucinous neoplasm (IPMN) is difficult to distinguish from low grade IPMN. The aim of this study was to identify potential markers for the discrimination of high grade and invasive IPMN from low and moderate grade IPMN. Experimental Design: Laser capture microdissection was used to isolate distinct foci of low grade, moderate grade, high grade, and invasive IPMN from paraffin embedded archival tissue from 14 patients who underwent resection for IPMN. Most samples included multiple grades in the same specimen. Affymetrix Human Exon microarrays were used for gene expression analysis to compare low and moderate grade (LMD) IPMN to high grade and invasive (HgInv) IPMN. Results: When comparing samples of LMD dysplasia (n=15) to those demonstrating HgInv (n=13), 62 genes were identified as showing significant changes in expression (p≤0.05 and a 2-fold cutoff), with up-regulation of 41 in HgInv IPMN and down-regulation in 21. Changes in gene expression are associated with biological processes related to malignant behavior including cell motion, cell proliferation, response to hypoxia, and epithelial to mesenchymal transition. Hierarchical clustering analysis demonstrated the ability of these 62 differentially expressed genes to distinguish between LMD and HgInv samples. In addition, altered signaling in several TGFβ-related pathways was exhibited in the progression of IPMN to malignancy. Conclusions: This study identifies a set genes associated with the progression of IPMN to malignancy. These genes are potential markers that could be used to identify IPMN requiring surgical resection. Using laser capture microdissection, distinct foci of low (n=10), moderate (n=5), and high grade dysplasia (n=6) as well as invasive carcinoma (n=7) were isolated from paraffin embedded archival tissue of 14 patients who underwent resection for IPMN. Gene expression data from Affymetrix Human Exon 1.0ST microarrays was utilized to compare low and moderate grade IPMN to high and invasive IPMN.

Dataset Information

Tumor-associated Neutrophils and Malignant Progression in Intraductal Papillary Mucinous Neoplasms: An Opportunity for Identification of High-risk Disease.

Publications

Tumor-associated Neutrophils and Malignant Progression in Intraductal Papillary Mucinous Neoplasms: An Opportunity for Identification of High-risk Disease.

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