Molecular analysis of single isolated glands in gastric cancers and their surrounding gastric intestinal metaplastic mucosa.

The biological properties and underlying genetics of gastric cancer and gastric intestinal metaplasia evolve with neoplastic progression from the genetics of the original gland cell. PCR assay with crypt isolation was used in tumors from 20 patients to examine microsatellite alterations (allelic imbalance at 17p, 5q, 18q, 3p, 4p, and 9p, and microsatellite instability) in glands from each tumor and from intestinal metaplastic lesions. Tumor specimens were processed as either pooled-gland samples or single-gland samples. Pooled gland sample was composed of 10-20 tumor glands, intestinal metaplastic glands, or nonmetaplastic glands. Single gland sample was 10 tumor glands from tumor and single gland sample was 5 gastric intestinal metaplastic and 5 nonmetaplastic glands from its surrounding metaplastic mucosa. Multiple genetic alterations were found in individual tumor glands, with various subclonal expansions seen within the same tumor. Although microsatellite instability was found in 2 of 20 tumor single-gland samples, none was detected in metaplastic single-gland samples. Most cancers appear to have a heterogeneous composition. On the other hand, microsatellite alterations were also detected within the nonmetaplastic as well as intestinal metaplastic single-gland samples. In conclusion, the present data on tumor and corresponding intestinal metaplastic and nonmetaplastic glands suggest that genetic alterations already occur within the surrounding of the noncancerous mucosa.