MULTIPLE HYPERPLASTIC POLYPS IN THE STOMACH - EVIDENCE FOR CLONALITY AND NEOPLASTIC POTENTIAL

The origin and neoplastic potential of gastric epithelial polyps remai ns an area of great interest, and treatment choices are a topic of con troversy. This report describes a patient diagnosed with three concurr ent hyperplastic gastric polyps that were studied for genetic alterati ons. The polyps were investigated for alterations in the K-ras oncogen e and the p53 tumor suppressor gene and for p21(WAF1/Cip1) and MDM2 pr otein overexpression. In addition, loss of heterozygosity at several l oci that are frequently involved in human cancer was analyzed, microsa tellite instability, a hallmark of the ''mutator'' phenotype, was dete rmined, and Epstein-Barr virus infection was investigated. All separat e areas from the three independent polyps harbored the same activating point mutation in codon 12 of the K-ras oncogene, indicating a clonal origin. DNA sequence alterations in p53 were not found, although high p53 protein levels could be shown by immunohistochemistry in areas of carcinoma within the largest polyp. No alterations in any of the othe r molecular markers were observed. The results strongly favor a clonal origin of the three independent gastric polyps and support the notion that these hyperplastic polyps may carry a risk for malignancy.