ABSENCE OF PEPSINOGEN A3 GENE-EXPRESSION IN THE GASTRIC-MUCOSA OF PATIENTS WITH GASTRIC-CANCER

Aims-To investigate the expression of pepsinogen A3 (Pg3) encoding gen es in the gastric mucosa of normal controls and subjects with atrophic gastritis and gastric cancer. Methods-One hundred and fifty nine pati ents underwent upper gastrointestinal endoscopy with sampling of gastr ic biopsy specimens and serum. Pg3 isoproteins were determined by elec trophoresis in serum and gastric mucosal biopsy specimens. Pg3 encodin g genes were assessed by PCR in DNA obtained from peripheral blood. Re sults-One hundred and one subjects (82 normal histology/chronic gastri tis, 17 atrophic gastritis, two gastric cancer) showed a pepsinogen ph enotype with presence of Pg3 and a corresponding pepsinogen genotype w ith presence of Pg3 encoding genes. Fifty eight subjects showed a phen otype lacking Pg3. In 39 of them (23 normal histology/chronic gastriti s, 11 atrophic gastritis, five gastric cancer), a corresponding genoty pe without Pg3 encoding genes was found. However, in the remaining 19 subjects (4 normal histology/chronic gastritis, nine atrophic gastriti s, six gastric cancer), Pg3 encoding genes were demonstrable in the ab sence of Pg3 production. Conclusions-Unexpressed Pg3 encoding genes ca n be shown in many cases of atrophic gastritis and gastric cancer, but rarely in healthy controls and subjects with superficial gastritis. T he correlation of atrophic gastritis and gastric cancer with a pepsino gen phenotype lacking Pg3 can be explained by loss of expression of Pg 3 encoding genes throughout the complete gastric mucosa. The mechanism of such loss and the importance as a marker for premalignant degenera tion have to be elucidated.