Gastric cancer screening by combined assay for serum anti-Helicobacter pylori IgG antibody and serum pepsinogen levels — “ABC method”

The current status of screening for gastric cancer-risk (gastritis A, B, C, D) method using combined assay for serum anti-Helicobacter pylori (Hp) IgG antibody and serum pepsinogen (PG) levels, “ABC method”, was reviewed and the latest results of our ongoing trial are reported. It was performed using the following strategy: Subjects were classified into 1 of 4 risk groups based on the results of the two serologic tests, anti-Hp IgG antibody titers and the PG I and II levels: Group A [Hp(−)PG(−)], infection-free subjects; Group B [Hp(+)PG(−)], chronic atrophic gastritis (CAG) free or mild; Group C [Hp(+)PG(+)], CAG; Group D [Hp(−)PG(+)]), severe CAG with extensive intestinal metaplasia. Continuous endoscopic follow-up examinations are required to detect early stages of gastric cancer. Asymptomatic Group A, which accounts for 50–80% of all the subjects may be excluded from the secondary endoscopic examination, from the viewpoint of efficiency. Hp-infected subjects should be administered eradication treatment aimed at the prevention of gastric cancer

Methylation and expression of human pepsinogen genes in normal tissues and their alteration in stomach cancer

In normal human tissues, pepsinogen A mRNA was expressed only in the fundic mucosa of the stomach, whereas pepsinogen C mRNA was expressed in all regions of the stomach mucosa and also in the proximal duodenal mucosa. The distributions of these mRNAs were consistent with those of pepsinogens A and C in the gastroduodenal mucosa. Methylation analysis of DNAs from normal tissues with methylation-sensitive restriction enzymes, HpaII and HhaI, revealed that pepsinogen A and C genes are hypomethylated in tissues producing pepsinogens A and C, suggesting a role of DNA methylation in the regulation of the differential expression of the genes for the two human pepsinogens during normal differentiation. In stomach cancer tissues and cancer cell lines, the expressions of the pepsinogen genes were decreased or lost, in good accordance with their pepsinogen productions. No gross structural changes of the pepsinogen genes were observed in these cancers, but the methylation patterns of the pepsinogen genes were found to be altered in different ways in different cancers. The functional significance of the altered methylation is unknown; however, these results suggest that considerable heterogeneity of the methylation patterns occurs in human stomach cancers.link_to_subscribed_fulltex