THE MULTIPLE ENDOCRINE NEOPLASIA TYPE-I GENE LOCUS IS INVOLVED IN THEPATHOGENESIS OF TYPE-II GASTRIC CARCINOIDS

Background & Aims: Both gastrin and genetic factors were suggested to underlie the pathogenesis of multiple gastric enterochromaffin-like (E CL) cell carcinoids, To assess the role of genetic alterations in carc inoid tumorigenesis, loss of heterozygosity (LOH) at the locus of the multiple endocrine neoplasia type 1 (MEN-1) gene was studied in gastri c carcinoids of patients with MEN-1 and chronic atrophic type A gastri tis (A-CAG), as well as in sporadically arising intestinal carcinoids, Methods: DNA extracted from archival tissue sections of 35 carcinoid tumors was assessed for LOH with eight polymorphic markers on chromoso me 11q13. A combined tumor and family study was performed in 1 patient with MEN-1-Zollinger-Ellison syndrome (ZES), Results: LOH at 11q13 lo ci was detected in 15 of 20 (75%) MEN-1-ZES carcinoids, and each ECL-c ell carcinoid with LOH showed deletion of the wildtype allele. Only 1 of 6 A-CAG carcinoids displayed LOH at the MEN-1 gene locus, and none of the 9 intestinal and rectal carcinoids showed 11q13 LOH, Conclusion s: Gastric ECL-cell carcinoid is an independent tumor type of MEN-1 th at shares a common developmental mechanism (via inactivation of the ME N-1 gene) with enteropancreatic and parathyroid MEN-1 tumors. Further analysis of sporadic and A-CAG carcinoids is needed to elucidate genet ic factors involved in their tumorigenesis.