MICROSATELLITE INSTABILITY IN PRECANCEROUS LESIONS AND ADENOCARCINOMAS OF THE STOMACH

BACKGROUND. It is generally known that replication errors (RERs) at mi crosatellite loci detected in human malignancies reflect a genetic ins tability that is caused by abnormalities of DNA mismatch repair system and underlie human carcinogenesis. The authors analyzed RERs in preca ncerous lesions and adenocarcinomas of the stomach to learn when genet ic instability occurs in stomach carcinogenesis. In addition, the auth ors examined genetic alterations of the p53 and adenomatous polyposis coli (APC) genes to investigate the correlation between genetic instab ility and genetic alterations in these tumor suppressor genes. METHODS . The authors examined microsatellite assay at 9 microsatellite loci i n 24 sporadic gastric cancers, 12 gastric adenomas, and 9 intestinal m etaplasia mucosae of the stomach from patients with gastric cancers us ing fresh frozen or formalin fixed and paraffin embedded samples paire d with normal mucosae. They also screened loss of heterozygosity (LOH) of the p53 and APC genes by polymerase chain reaction-restriction fra gment length polymorphism (PCR-RFLP) analysis. RESULTS. In total, the RER(+) phenotypes were observed in 8 of 24 (33%) gastric cancers, 5 of 12 (42%) gastric adenomas, and 3 of 9 (33%) intestinal metaplasia muc osae of the stomach. Histologically, RERs were detected in 3 of 9 (33% ) well differentiated adenocarcinomas, 2 of 11 (18%) poorly differenti ated adenocarcinomas, and 3 of 4 (75%) scirrhous type gastric cancers respectively. Several cases showed RERs at many microsatellite loci si multaneously. Some RER(+) phenotypes had genetic alterations of the p5 3 or APC genes detected by LOH using PCR-RFLP analysis. However, no si gnificant correlation was found between RER(+) phenotypes and LOH in t hese genes. CONCLUSIONS. The frequency of RERs in detected gastric can cers were almost the same when compared with previously reported data. Interestingly, RERs were detected in greater than 30% of precancerous lesions, suggesting that genetic instability is an early somatic even t of multistep stomach carcinogenesis. It also suggests that the adeno ma-carcinoma sequence does exist in stomach carcinogenesis, espe ciall y in well differentiated adenocarcinomas. Moreover, alterations in the p53 and APC genes detected by PCR-RFLP analysis did not correlate wit h RER(+) phenotypes. (C) 1996 American Cancer Society.