Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

Pancreatic ductal adenocarcinoma continues to be one of the most difficult diseases to manage with one of the highest cancer mortality rates. This is due to several factors including nonspecific symptomatology and subsequent diagnosis at an advanced stage, aggressive metastatic behavior that is inco...

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Veröffentlicht in:Modern pathology 2015-11, Vol.28 (11), p.1470-1480
Hauptverfasser: Drifka, Cole R, Tod, Jo, Loeffler, Agnes G, Liu, Yuming, Thomas, Gareth J, Eliceiri, Kevin W, Kao, W John
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container_issue 11
container_start_page 1470
container_title Modern pathology
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creator Drifka, Cole R
Tod, Jo
Loeffler, Agnes G
Liu, Yuming
Thomas, Gareth J
Eliceiri, Kevin W
Kao, W John
description Pancreatic ductal adenocarcinoma continues to be one of the most difficult diseases to manage with one of the highest cancer mortality rates. This is due to several factors including nonspecific symptomatology and subsequent diagnosis at an advanced stage, aggressive metastatic behavior that is incompletely understood, and limited response to current therapeutic regimens. As in other cancers, there is great interest in studying the role of the tumor microenvironment in pancreatic ductal adenocarcinoma and whether components of this environment could serve as research and therapeutic targets. In particular, attention has turned toward the desmoplastic collagen-rich pancreatic ductal adenocarcinoma stroma for both biological and clinical insight. In this study, we used quantitative second harmonic generation microscopy to investigate stromal collagen organization and structure in human pancreatic ductal adenocarcinoma pathology tissues compared with non-neoplastic tissues. Collagen topology was characterized in whole-tissue microarray cores and at specific pathology-annotated epithelial–stroma interfaces representing 241 and 117 patients, respectively. We quantitatively demonstrate that a unique collagen topology exists in the periductal pancreatic ductal adenocarcinoma stroma. Specifically, collagen around malignant ducts shows increased alignment, length, and width compared with normal ducts and benign ducts in a chronic pancreatitis background. These findings indicate that second harmonic generation imaging can provide quantitative information about fibrosis that complements traditional histopathologic insights and can serve as a rich field for investigation into pathogenic and clinical implications of reorganized collagen as a pancreatic ductal adenocarcinoma disease marker.
doi_str_mv 10.1038/modpathol.2015.97
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subjects 13/105
14/69
631/67/1857
692/53
Area Under Curve
Carcinoma, Pancreatic Ductal - pathology
Collagen - ultrastructure
Humans
Immunohistochemistry
Laboratory Medicine
Medicine
Medicine & Public Health
Microscopy, Confocal
original-article
Pancreatic Neoplasms - pathology
Pancreatitis, Chronic - pathology
Pathology
ROC Curve
Sensitivity and Specificity
Tissue Array Analysis
Tumor Microenvironment
title Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis
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