Identification of Paneth cells in pyloric glands associated with gastric and intestinal mixed-type intestinal metaplasia of the human stomach

Abstract

We have proposed that intestinal metaplasia (IM) of the human stomach be divided into two types on the basis of cell differentiation status: a gastric and intestinal (GI) mixed type and a solely intestinal (I) type. In the GI mixed type, gastric (foveolar epithelial and pyloric gland cells) and intestinal (goblet, intestinal absorptive, and Paneth cells) phenotype cells coexist in the same intestinalized gastric glands in various combinations and degrees. Consequently, intestinalized gastric glands are hybrids. Although we have described the rare appearance of Paneth-like cells in pyloric glands of GI mixed-type IM, the absence of an appropriate Paneth cell marker leaves room for doubt as to their true character. The purpose of this study was to clearly identify Paneth cells in pyloric glands in IM lesions using a new Paneth cell marker, a polyclonal antibody human defensin (HD)-5, raised against HD-5, which is included in granules of Paneth cells. A total of 105 gastric samples (4 biopsy and 101 surgical resected specimens) were examined. In only nine cases (8.6%), the antibody allowed demonstration of Paneth cells in pyloric glands in GI mixed-type IM, confirming our previous finding. Analysis of the proliferative cell (P) zone indicated that a common stem cell might generate both GI phenotype cells by upward and downward migration. No Paneth cells were found above the P zone. The results suggest that the stem cells show abnormal cell differentiation in IM lesions but preserve their normal direction of migration.

Differential gene-expression profiles associated with gastric adenoma

“…LI-Cadherin is usually expressed in normal intestinal mucosa and ectopically in well-differentiated gastric adenocarcinomas (Grotzinger et al, 2001). Defensin alpha 5 consists of a family of antimicrobial peptides that are highly expressed in small intestinal Paneth cells (Inada et al, 2001). The defensin family has alternative functions, such as promotion of cell differentiation (Frye et al, 2001).…”

Gastric-and-intestinal mixed-type intestinal metaplasia: aberrant expression of transcription factors and stem cell intestinalization

“…In the normal intestinal gland, cells that will become absorptive and goblet cells move up, and only those differentiating into Paneth cells migrate lower from the proliferative cell zone. In GI mixed-type IM, gastric surface mucous cells, intestinal absorptive cells, and goblet cells are found in the glandular portions above the proliferative zone, while pyloric gland cells and Paneth cells are found in the lower glandular portions, below the proliferative zone [40]. GI mixed-type IM may be the consequence of the abnormal differentiation of stem cells that can produce both gastric-and intestinal-type cells, with the normal cell migration pattern preserved.…”

Expression of Cdx1 and Cdx2 mRNAs and relevance of this expression to differentiation in human gastrointestinal mucosa — with special emphasis on participation in intestinal metaplasia of the human stomach

“…With the stomach, mucosa adjacent to lesions was also fixed in 10% buffered formalin solution and embedded in paraffin for histological examination. Sections were stained with H&E, and then assessed by microscopy to determine the degree of IM, which was classified as mild, moderate, and severe, as previously described [21]. Five specimens were obtained from each IM region with mild IM and four specimens were obtained from each IM region with severe IM.…”