Alterations of gastric homeoprotein expression in H. Pylori infection and/or intestinal metaplasia

Abstract

Background and aim: Homeoproteins, which are essential for growth and development, are often aberrantly expressed in cancer. Helicobater pylori is a class I carcinogen. However, whether aberrant expression of homeoproteins is associated with H. pylori infection is rarely investigated. The aim of this study was to determine the expression of homeoproteins CDX2, PDX-1, PAX6, and NKX6.1 in gastric mucosa with or without H. pylori infection and/or intestinal metaplasia (IM). Methods: Gastric biopsy specimens from antrum, incisura and body of 98 patients (43 males, 55 females; age, 45.815.7) with nonulcer dyspepsia were used for the detection of histopathological changes and the expression of homeoproteins CDX2, PDX-1, PAX6, and NKX6.1 by immunohistochemistry. H. pylori infection was defined to be present when both histology and the rapid urease test were positive. Cytoplasmic and nuclear immunostaining of the homeoproteins in the gastric mucosa were scored separately according to the proportion of stained area and the staining intensity. Results: Expression of the homeoproteins was detectable in gastric mucosa. In gastric antrum and incisura, the scores of cytoplasmic and/or nuclear expression of PDX-1, PAX 6, and NKX6.1 in H. pylori infected patients were significantly less than those in uninfected patients (p 0.01), while the score of nuclear expression of CDX2 at the body in H. pylori infected patients was more than that in the uninfected patients (p 0.05). In the presence of IM, gastric nuclear CDX2 expression was up-regulated (p 0.05), whereas cytoplasmic expression of PDX-1, PAX 6, and NKX6.1 at the incisura was down-regulated (p 0.05). However, in a multivariate analysis using logistic regression, IM was independently associated with increased nuclear expression of CDX2, whereas H. pylori infection was independently associated with decreased cytoplasmic expression of PDX-1, PAX 6 and NKX6.1. Conclusions: Nuclear CDX2 expression in the whole stomach was up-regulated in patients with IM, regardless of H. pylori infection, while cytoplasmic expression of PDX-1, PAX 6 and NKX6.1 at gastric antrum and incisura was down-regulated in the presence of H. pylori infection.