'Senescence-associated' beta-galactosidase activity in the upper gastrointestinal tract.

Abstract

Beta-galactosidase activity at pH 6 is associated in vitro with senescence and cellular death, but in vivo data are sparse. This study undertook firstly to map 'senescence-associated' beta-galactosidase activity (SAbetaG) at pH 6 in normal epithelia and mucosae of the upper gastrointestinal tract. As escape from senescence confers a proliferative advantage, a reduction in SAbetaG activity might be predicted in neoplasia and their precursors in vivo. This prediction was tested in metaplastic, dysplastic, and neoplastic epithelium of the upper gastrointestinal tract. Histochemical staining for SAbetaG was performed at pH 6 on cryostat sections of 350 endoscopic biopsies from sites including oesophagus, stomach, and duodenum of 46 patients: 28 with Barrett's oesophagus (two with adenocarcinoma), 15 with gastric adenocarcinoma, and three with oesophageal squamous cancer. A staining score (range 0-6) was assigned to epithelial cells in all mucosae and scores were calculated for surface (luminal), intermediate, and deep (basal) layers. The strongest SAbetaG activity was in surface luminal cells of normal duodenal mucosa (mean score 3.6+/-0.5; n=19), 'specialized' Barrett's mucosa (mean 2.2+/-0.12; n=105), and intestinal metaplasia in the stomach (mean 2.4+/-0.40; n=16). Squamous epithelium was consistently negative for SAbetaG activity. Low- and high-grade Barrett's dysplasia showed no decrease in SAbetaG activity, but reduced activity was seen in gastric and oesophageal adenocarcinomas (mean 1.24+/-0.29; n=17; p=0.012). In six gastric adenocarcinomas, there was no detectable activity. Whether SAbetaG is truly a marker of cellular senescence in vivo remains to be determined. Activity is low in mucosal proliferation compartments and increases with cellular differentiation, especially in native or metaplastic intestinal mucosae. SAbetaG activity persists in dysplastic mucosae but may show some reduction or loss in adenocarcinomas (p=0.0012). Loss of SAbetaG activity is not, therefore, an early event in glandular dysplasia-neoplasia of the upper gastrointestinal tract.