LOH AT THE APC MCC GENE (5Q21) IN GASTRIC-CANCER AND PRENEOPLASTIC LESIONS - PROGNOSTIC IMPLICATIONS/

The APC/MCC gene (Familial Adenomatous Polyposis) at 5q21 plays a role in colon cancer carcinogenesis. LOH at this locus has also been descr ibed in gastric cancer and preneoplastic lesions. The APC locus has be en recently related to a cell surface adhession molecule and its alter ation may favour metastatic dissemination. LOH at 5q21 has been associ ated with poor prognosis in other tumors such as lung cancer. Thirty-s ix gastric cancers were evaluated for LOH at 5q21 with 2 polymorphic m arkers from microdissected paraffin-embedded material. All tumors were classified by stage, histologic type, degree of differentiation and s urvival rates. In 4 cases, intestinal metaplasia cells in the adjacent mucosae were also microdissected. Six cases of moderate-severe gastri c dysplasia were also added to the study. LOH was determined in 84 % o f the informative cases of GC, affecting both early and advanced stage s of disease. Genomic instability was assessed in 5 cases, 3 of them a ssociated with LOH. The only case of gastric cancer that did not show LOH or instability at 5q21 was a stage II, poorly differentiated intes tinal carcinoma without evidence of recurrence after a 36 month follow -up period (the mean survival rate in our series was 28.3 % at 36 mont hs). We also found LOH in 2/6 dysplastic lesions and 1/4 intestinal me taplasias. Our data show that LOH at 5q21 is frequent in gastric cance r and is also present in intestinal metaplasia and dysplastic lesions. LOH at this locus is not a prognostic factor in GC in our study, due to the high incidence of LOH that we found.