Computer-aided assessment of the extra-cellular matrix during pancreatic carcinogenesis

a pilot study

Fabio Grizzi*, Sirio Fiorino, Dorina Qehajaj, Adele Fornelli, Carlo Russo, Dario De Biase, Michele Masetti, Laura Mastrangelo, Matteo Zanello, Raffaele Lombardi, Andrea Domanico, Esterita Accogli, Andrea Tura, Leonardo Mirandola, Maurizio Chiriva-Internati, Robert S. Bresalier, Elio Jovine, Paolo Leandri, Luca Di Tommaso

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number61
Pages (from-to)1-9
Number of pages9
JournalJournal of Translational Medicine
Volume17
Issue number1
DOIs
Publication statusPublished - 28 Feb 2019
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Degradation
  • Extra-cellular matrix
  • Fractals
  • Modeling
  • Pancreatic adenocarcinoma

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