Gastric PDX-1 expression in pancreatic metaplasia and endocrine cell hyperplasia in atrophic corpus gastritis

Abstract

The homeodomain transcription factor PDX-1 plays a key role in endocrine and exocrine differentiation processes of the pancreas. PDX-1 is also essential for differentiation of endocrine cells in the gastric antrum. The role of PDX-1 in the pathogenesis of endocrine cell hyperplasia and pancreatic metaplasia in corpus and fundus gastritis has not been evaluated. By immunohistochemistry and double-immunofluorescence, we investigated the expression of PDX-1 in 10 tissue specimens with normal human gastric mucosa, nonatrophic and atrophic gastritis and in pancreatic metaplasia, respectively. In normal corpus mucosa and in nonatrophic corpus gastritis, PDX-1 was mainly absent. In pancreatic metaplasia, PDX-1 was found in metaplastic cells and in adjacent gastric glands. In contrast to normal gastric corpus mucosa, PDX-1 could be strongly detected in the cytoplasm of the parietal cells surrounding metaplastic areas. Furthermore, PDX-1 expression was found in hyperplastic endocrine cells and in the surrounding gastric glands in chronic atrophic gastritis. Hyperplastic endocrine cells coexpressed the b-subunit of the gastric H,K-ATPase. We conclude that PDX-1 represents a candidate switch factor for glandular exocrine and endocrine transdifferentiation in chronic gastritis and that an impaired parietal cell differentiation might play a key role in disturbed gastric morphogenic processes. Keywords: PDX-1; gastritis; gastric atrophy; pancreatic metaplasia; endocrine cell hyperplasia In recent years, several factors have been characterized that play a key role in pancreatic organogenesis. 1 The homeobox transcription factor PDX-1 (pancreatic duodenal homeobox-1) also termed IPF-1 could be regarded as master switch for glandular exocrine and endocrine differentiation in the pancreas. Mutations within the PDX-1 gene are associated with type II diabetes mellitus or even with pancreatic agenesis. 2 In the stomach, PDX-1 has been shown to be essential for the differentiation of endocrine cells in the antropyloric region of mice and targeted deletion of PDX-1 leads to severely impaired development of gastrin cells in the antrum. 3 However, no study concerning the potential role of PDX-1 in glandular differentiation processes of the oxyntic mucosa in the corpus and fundus region has been undertaken. In these areas, pancreatic (acinar) metaplasia is frequently found and is associated with chronic gastritis. 4,5 Histologically, this type of metaplasia is characterized by acinus-like nests of epithelial cells producing pancreatic enzymes such as amylase, lipase and trypsinogen. 4 Furthermore, the so-called hyperplastic endocrine nodules can be regularly found in severe atrophic corpus gastritis. These nodules represent precursor lesions for neuroendocrine tumors within the gastric mucosa. 6 The molecular pathogenesis of both, pancreatic metaplasia and endocrine cell hyperplasia, is only poorly understood. To investigate the potential role of PDX-1 in these pathological conditions within the glandular compartment of the gastric mucos...

PDX‐1

“…An opposite view has been mentioned in one study in which PDX-1 was considered as a tumor suppressor gene in human gastric cancer 45. Further studies are needed to clarify this issue, since most studies showed high level of PDX-1 in gastric cancer specimens46–50, as opposite to this study showing low expression of PDX-1 in a single human gastric cancer cell line.…”

Intestinal metaplasia: A premalignant lesion involved in gastric carcinogenesis

“…Shh is normally found at high levels in the proximal corpus of the human stomach. Its expression is lost in atrophic gastritis 61 and IM, 62 with lower expression levels being observed in incomplete versus the complete subtype 38 . Loss of shh is an early change in premalignant lesions which may also contribute to gastric cancer, although this may be due to its expression in parietal cells which are lost along the progression from atrophy to gastric cancer.…”

Pancreatic Metaplasia in the Gastro-achlorhydria in WTC-dfk Rat, a Potassium Channel Kcnq1 Mutant

“…Expression of PDX-1 has been reported in pancreatic metaplasia of the stomach in humans. 2,8 No positive reaction was observed in the pancreatic metaplasia of the stomach in the WTC-dfk rats by using immunohistochemical examination for PDX-1.…”