Computer-aided assessment of the extra-cellular matrix during pancreatic carcinogenesis: a pilot study

Journal of Translational Medicine

Adele Fornelli¹  Andrea Tura²  Robert S. Bresalier³  Dorina Qehajaj⁴  Fabio Grizzi⁴  Dario de Biase⁵  Luca Di Tommaso⁶  Paolo Leandri⁷  Sirio Fiorino⁷  Leonardo Mirandola⁸  Maurizio Chiriva-Internati⁸  Michele Masetti⁹  Matteo Zanello⁹  Elio Jovine⁹  Raffaele Lombardi⁹  Laura Mastrangelo⁹  Andrea Domanico^1,10  Esterita Accogli^1,10  Carlo Russo^1,11 

[1] Anatomic Pathology Service, Maggiore Hospital;CNR Institute of Neuroscience;Department of Gastroenterology, Hepatology & Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer;Department of Immunology and Inflammation, Humanitas Clinical and Research Center—IRCCS;Department of Pharmacy and Biotechnology (FaBiT), University of Bologna;Humanitas University;Internal Medicine Unit, Maggiore Hospital;Kiromic Biopharma, Inc.;Surgery Unit, Maggiore Hospital;Ultrasound Center Internal Medicine A, Maggiore Hospital;“Michele Rodriguez” Foundation-Institute for Quantitative Measures in Medicine;

关键词: Pancreatic adenocarcinoma;    Extra-cellular matrix;    Degradation;    Modeling;    Fractals;   

DOI  :  10.1186/s12967-019-1817-3

来源: DOAJ

【 摘 要 】

Abstract Background A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process. Methods A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method. Results We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal. Conclusion These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies.

【 授权许可】

Unknown