muramidase and Adenomatous-Polyposis-Coli

In the normal duodenal mucosa, differentiated cells (enterocytes, goblet cells and endocrine cells) migrate from stem cells to the tip of the villi, but the lysozyme-producing Paneth cells migrate to the bottom of the crypts. The position of the Paneth cells within duodenal adenomas was investigated.. Sections from 83 duodenal adenomas were stained with hematoxylin-eosin (H&E) and with anti-lysozyme. Mature Paneth cells were those showing coarse brightly red cytoplasmic granules in H&E stain whereas their precursors were the lysozyme-positive cells that were undetected by H&E.. The number of mature Paneth cells/high power field (x 40) varied in adenomas from 4 to 12 (mean 65) in H&E stain, while 32 to 62 cells/field (mean 46.5) were positive in anti-lysozyme immunostain (p < 0.05). The lysozyme-expressing cells were randomly distributed within the adenoma including the superficial cell layers.. Since mature Paneth cells and their precursors are positioned underneath stem cells, the presence of mature Paneth cells and their lysozyme-positive precursors in the surface epithelium of duodenal adenomas would imply that stem cells might have already exfoliated. An alternative explanation would mean that mutated stem cells, anchored in the bottom of the crypts of the adenoma would redirect, in an unparalleled fashion, the ontogenetic logistics of migration for Paneth cells. This stochastic molecular behaviour would require a reversal from the pre-determined migratory flow for Paneth cells to a paradoxical migration mode for these cells (from stem cells vertically along the villus, before exfoliation). Consequently, it is not inconceivable that stem cells might participate, together with other mature cells, in the cellular turnover of duodenal adenomas. If that is the case, the duodenal adenoma emerges as a suitable model to monitor the actual fate of mutated stem cells.

Topics: Adenoma; Adenomatous Polyposis Coli; Duodenal Neoplasms; Eosine Yellowish-(YS); Hematoxylin; Humans; Intestinal Mucosa; Muramidase; Neoplastic Stem Cells; Paneth Cells; Staining and Labeling

The authors have previously shown that duodenal adenomas in familial adenomatous polyposis (FAP) patients typically reveal abundant cells with endocrine differentiation (ED), Paneth differentiation (PD), and goblet cell differentiation (GD). However, the biological significance and proliferative potential of these cells is unknown. To study the proliferative properties of cells with ED, PD, or GD in FAP-associated duodenal adenomas, the authors used a double-labeling immunohistochemical technique to detect simultaneously the presence of proliferating cell nuclear antigen (PCNA), and either chromogranin or lysozyme in individual neoplastic cells. Adenomatous cells with GD were identified morphologically and also evaluated for the degree of PCNA expression by immunohistochemistry. Duodenal adenomas and the adjacent nonadenomatous epithelium from 10 FAP patients were studied. Cells with ED, PD, and GD were present in all adenomas, and constituted 14.1%, 11.6%, and 17.7% of adenomatous cells, respectively. The overall proliferative index of nondifferentiated adenomatous cells was 33.3%, which was similar to the proliferative index obtained for adenomatous cells with GD (31.2%) and nonadenomatous crypt goblet cells (34.9%). In contrast, adenomatous cells with ED and PD showed a significant decrease in their proliferative potential (P < .001). Only 6.0% and 7.3% of cells with ED and PD, respectively, were proliferative. Nonadenomatous crypt endocrine and Paneth cells showed no proliferative potential (proliferative index 0%). These results suggest that, in the process of proliferation and differentiation, specific subpopulations of adenomatous cells attempt to recapitulate the biological characteristics of their normal counterparts in the small intestinal crypts. Adenomatous cells with ED and PD are hypoproliferative, a finding that is consistent with their differentiated phenotype and suggests that these cells may not participate as actively in the growth of these lesions.

Topics: Adenoma; Adenomatous Polyposis Coli; Adult; Cell Differentiation; Cell Division; Chromogranins; Duodenal Neoplasms; Female; Humans; Immunoenzyme Techniques; Intestinal Mucosa; Male; Muramidase; Proliferating Cell Nuclear Antigen