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

Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis
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 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.
0893-3952
1470-1480
Drifka, Cole R.
4cd3cbff-cfb2-47dd-929c-befd3bf4d3f4
Tod, Joanne
d45d955c-c5dd-40e8-b0cd-f278be8e9f36
Loeffler, Agnes G
7d926c88-3db7-41b7-bc6d-7593e2f2cf2a
Liu, Yuming
0be47838-bf2a-4dbf-b2c3-a2b32eb872a7
Thomas, Gareth J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Eliceiri, Kevin W
2ab33d6a-4b62-42f0-a3fe-e4d1204a0d39
Kao, W. John
34a3c738-4e6c-40d5-98ab-72a22198f6c5
Drifka, Cole R.
4cd3cbff-cfb2-47dd-929c-befd3bf4d3f4
Tod, Joanne
d45d955c-c5dd-40e8-b0cd-f278be8e9f36
Loeffler, Agnes G
7d926c88-3db7-41b7-bc6d-7593e2f2cf2a
Liu, Yuming
0be47838-bf2a-4dbf-b2c3-a2b32eb872a7
Thomas, Gareth J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Eliceiri, Kevin W
2ab33d6a-4b62-42f0-a3fe-e4d1204a0d39
Kao, W. John
34a3c738-4e6c-40d5-98ab-72a22198f6c5

Drifka, Cole R., Tod, Joanne, Loeffler, Agnes G, Liu, Yuming, Thomas, Gareth J., Eliceiri, Kevin W and Kao, W. John (2015) Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis. Modern Pathology, 28 (11), 1470-1480. (doi:10.1038/modpathol.2015.97). (PMID:26336888)

Record type: Article

Abstract

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.

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Accepted/In Press date: 16 July 2015
e-pub ahead of print date: 4 September 2015
Published date: November 2015
Organisations: Cancer Sciences, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 395568
URI: https://eprints.soton.ac.uk/id/eprint/395568
ISSN: 0893-3952
PURE UUID: 2fb92630-368e-4e32-b846-37d9d19076ff

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Date deposited: 01 Jun 2016 13:29
Last modified: 17 Jul 2017 18:53

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Contributors

Author: Cole R. Drifka
Author: Joanne Tod
Author: Agnes G Loeffler
Author: Yuming Liu
Author: Kevin W Eliceiri
Author: W. John Kao

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