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

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.

Rapid acceleration of KRAS-mutant pancreatic carcinogenesis via remodeling of tumor immune microenvironment by PPARδ

“…1e, f ). Furthermore, the PPARδ upregulation was associated with a progressive increase of KRAS mu activity (measured by p-Erk1/2 IHC), ductal metaplasia (Alcian blue staining for acidic mucins 28 ), and pancreatic fibrosis (Sirius red staining for collagen fibrils 29 ) (Fig. 1e, f , Supplementary Fig.…”

Ppard Is Essential in Acceleration of Pancreatic Ductal Adenocarcinoma Development by High-Fat Diet in MutantKrasMice

“…1E and F). Histologic examinations of the KC mouse tissues showed that compared to the adjacent normal pancreatic tissues, PanINs had higher expression levels of p-ERK1/2, an indicator for aberrant oncogenic Kras activation, as measured by IHC staining, higher levels of acidic mucins, as stained by Alcian blue 28 ; and more pancreatic fibrosis, as shown by Sirius red staining for collagen fibrils 29 (Fig. 1E).…”

Ablation of palladin in adult heart causes dilated cardiomyopathy associated with intercalated disc abnormalities

“…Briefly, heart sections were stained with hematoxylin and eosin or Picro Sirius Red and imaged using a VS20 DotSlide Digital Virtual Microscopy System (Olympus). The area of fibrosis in the LV was determined using ad hoc software automatically detecting Picro Sirius Red-stained areas based on RGB color segmentation ( Grizzi et al, 2019 ). The sum of Picro Sirius Red-stained areas was expressed as a percentage of the LV area excluding unfilled and tissue-free spaces.…”