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.
Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA.|Laboratory for Optical and Computational Instrumentation, University of Wisconsin, Madison, WI, USA.
Cole R
CR
Drifka
Cancer Sciences Unit, University of Southampton, Southampton, UK.
Jo
J
Tod
Department of Pathology, University of Wisconsin, Madison, WI, USA.|Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI, USA.
Agnes G
AG
Loeffler
Laboratory for Optical and Computational Instrumentation, University of Wisconsin, Madison, WI, USA.
Yuming
Y
Liu
Cancer Sciences Unit, University of Southampton, Southampton, UK.
Gareth J
GJ
Thomas
Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA.|Laboratory for Optical and Computational Instrumentation, University of Wisconsin, Madison, WI, USA.|Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI, USA.
Kevin W
KW
Eliceiri
Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA.|Laboratory for Optical and Computational Instrumentation, University of Wisconsin, Madison, WI, USA.|Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI, USA.|Department of Surgery, University of Wisconsin, Madison, WI, USA.|School of Pharmacy, University of Wisconsin, Madison, WI, USA.
W John
WJ
Kao
D019540:Area Under Curve; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D003094:Collagen / Q000648:ultrastructure*; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D010190:Pancreatic Neoplasms / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000473:pathology*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
D003094:Collagen