Numerous recent studies demonstrate gastrinomas, similar to carcinoid tumors and all other pancreatic endocrine tumors (PET's) except insulinomas, usually (60-90%) are malignant and some may have an aggressive course. The natural history of these tumors is largely undefined and the molecular pathogenesis, not only for the tumors themselves, but also for determining their growth behavior is almost completely unknown. Recent studies demonstrate that in contrast to many other more common cancers neither oncogenes nor common tumor suppressor genes (p53, retinoblastoma, VHL gene, etc.) are generally altered in gastrinomas, carcinoids or other PET's. To define the natural history of gastrinomas, the clinical, laboratory and tumor characteristics [primary tumor location, tumor extent, tumor growth pattern, development of a secondary tumor syndrome (Cushings, etc.), tumor metastatic pattern] on 212 patients prospectively followed at NIH have been collected and entered into a data base which is being prospectively updated. This analysis has identified a cohort of 25% of patients in whom gastrinomas pursued an aggressive clinical course. Both clinical and laboratory characteristics that distinguish patients with an aggressive course are being sought by statistical analysis as well as correlations with possible molecular changes in the gastrinoma that may correlate with prognosis and tumor growth. The frequency and prognostic value of alterations in the gene for Multiple Endocrine Neoplasia-type 1 (MEN1) and the tumor suppressor gene, p16, are currently being investigated, as well as the importance of overexpression of growth factors and their receptors in gastrinomas, the predictive value of proliferating cell antigens (Ki-67, etc.) and the possible identification of important other alterations in determining prognosis using genomic-wide allelotyping.
