Regulation of apoptosis is impaired in atrophic gastritis associated with gastric cancer

BACKGROUND: Gastric premalignant conditions, atrophic gastritis (AG) and intestinal metaplasia (IM) are characterized by an increase of proliferation and a reduction of apoptosis in epithelial cells. The epithelial cell kinetics in AG and IM in gastric mucosa adjacent to gastric cancer is still unclear. The aim of this study was to evaluate the epithelial cell turnover and expression of proliferation and apoptosis-related genes in gastric cancer (GC) and adjacent mucosa with atrophic gastritis or intestinal metaplasia (AG/IM GC+), as well as in atrophic gastritis or intestinal metaplasia mucosa of patients without GC (AG/IM GC-) and in control biopsy samples of non-transformed gastric mucosa (Control). METHODS: We selected 58 patients (M: F = 34:24; age range 20-84 years, median 61.06 years) with 4 well defined histological conditions: 20 controls with histological finding of non-transformed gastric mucosa, 20 patients with AG or IM (AG/IM GC-), and 18 patients with intestinal type gastric adenocarcinoma (GC) and AG or IM in the adjacent mucosa (3 cm from the macroscopic tumour margin, AG/IM GC+). We performed an immunohistochemical staining of Ki67 and TUNEL and quantitative RT-PCR to determine the expression of PCNA and Bax/Bcl-2. RESULTS: The immunohistochemical expression of Ki67 and TUNEL in AG/IM GC- was significantly increased compared to not transformed gastric mucosa (p < 0.0001) but not compared to AG/IM in gastric mucosa adjacent to GC. Levels of Bcl-2 were reduced in GC and AG/IM GC- compared to controls as well as in AG/IM GC- compared to AG/IM in mucosa adjacent to GC+ (p < 0.05). Proliferation and apoptosis markers did not correlate with H.pylori status in our study population. CONCLUSIONS: In AG/IM associated with GC, no significant changes in the epithelial cell turnover were detected. Decreased Bcl-2 gene expression signified atrophic gastritis and IM in presence of cancer, as well as intestinal type gastric adenocarcinoma.