Pathomorphological characteristics of the restructuring of acinar-insular tissue with severe fibrosis of the pancreas in patients with chronic pancreatitis
DOI:
https://doi.org/10.14739/2310-1237.2013.2.17798Keywords:
fibrosis of the pancreas, the restructuring of acinar tissue, chronic pancreatitisAbstract
The regression of acinar tissue and endocrine apparatus of the pancreas in chronic pancreatitis with severe pancreatic fibrosis was studied.
The aim of the research: microscopical and immunohistochemical analysis of the restructuring of pancreatic acinar-islet tissue with severe fibrosis of the pancreas in patients with chronic pancreatitis.
Materials and methods. Histological, immunohistochemical (Ki-67, caspase-3, MMP-9, TIMP-1, СА 19-9, collagen III and IV types), morphometric studies (Image J program) and statistical analysis were carried out on biopsies of the pancreas of 20 patients (30-72 years old) with CP.
Results. Only small foci of intact exocrine tissue are observed in severe pancreatic peri-tubular, inter-and intralobular fibrosis of pancreas in patients with chronic pancreatitis. Expanded large pancreatic ducts, narrowed and partially obliterated arteries, zones of active restructuring of acinar tissue, formed tubular complexes and tubular-insular complexes are determined in extensive fibrous fields.
In areas of active restructuring of acinar tissue the level of expression of the proliferation marker Ki-67 of pancreatic cells is significantly higher, more than twice, than in the zones formed of tubular and tubular-insular complexes (2,38 ± 0,52 points against 1,0 ± 0,60, p <0.05), and much higher than in the pancreas of patients from control group.
In severe pancreas fibrosis activation of apoptosis of acinar, islet and tubular cells is mostly significant in the areas of active restructuring of acinar tissue: in these zones a moderate level of expression of caspase-3 in pancreatic cells is determined in 62% of patients, mild expression level of expression of caspase-3 - in 38% of patients. In the zones formed of tubular and tubular-insular complexes moderate level of expression of caspase-3 in pancreatic cells is determined in 33% of patients, mild level of expression - in 42% of patients and in 25% of patients the expression of caspase-3 is not detected in these pancreatic areas.
Increased levels of pancreatic cells’ MMP-9 are detected in the areas of active restructuring of acinar tissue in comparison with expression of metalloproteinases in the zones of formed tubular complexes and tubular-insular complexes in patients with severe fibrosis. At the same time the areas of active restructuring of acinar tissue and formed tubular complexes and tubular-insular complexes show very mild expression of TIMP-1. These zones show direct relationship of medium strength (Pearson’s r = +0,62) between the area of MMP-9 expression and immunopositive area of collagen type III and the inverse relationship of medium strength (Pearson’s r =–0,55) between the area of MMP-9 expression and immunopositive area of collagen type IV.
Conclusion. In patients with chronic pancreatitis, with the development of stenosis and obliteration of the pancreatic arteries, peri-and intralobular fibrosis in areas of active restructuring of acinar pancreatic tissue increases apoptosis in pancreatic acinar cells, which is partially offset by the proliferation of new generations and new formation of small terminal ducts. On the background of significant level of MMP-9 expression and very mild level of TIMP-1 expression development of severe peri-intralobular fibrosis is accompanied by replacement of ordered molecular fibrous matrix of the basement membranes of acini by fibrillar collagen types I and III, the loss of acinar tissue and the appearance of functionally invalid tubular complexes and tubular-insular complexes with functioning islets of Langerhans on its place.
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