Pathophysiology of Gastric NETs: Role of Gastrin and Menin

Abstract

Neuroendocrine tumors (NETs) were initially identified as a separate entity in the early 1900s as a unique malignancy that secretes bioactive amines. GI-NETs are the most frequent type, and represent a unique subset of NETs because at least 75% of these tumors represent gastrin stimulation of the enterochromaffin-like cell located in the body of the stomach. Purpose of Review To understand the specific role of gastrin in the generation of Gastric NETs (G-NETs). Recent Findings We review here the origin of enterochromaffin cells gut and the role of hypergastrinemia in gastric enteroendocrine tumorigenesis. We describe generation of the first genetically engineered mouse model of gastrin-driven G-NETs that mimics the human phenotype. The common mechanism observed in both the hypergastrinemic mouse model and human carcinoids is translocation of the cyclin-dependent inhibitor p27kip to the cytoplasm and its subsequent degradation by the proteasome. Summary Therapies that block degradation of p27kip, the CCKBR2 gastrin receptor or gastrin peptide are likely to facilitate treatment.

The Diagnosis of Neuroendocrine Tumours: An Endocrine Perspective

“…There are three types of gastric NETs: type I gastric NETs represent around 70-80% and are associated with chronic atrophic gastritis (85). Partial or complete atrophy of parietal cells lead to hypo-or achlorhydria.…”

“…Premature graying of the hair, anti-parietal cell or intrinsic factor antibodies, pernicious anemia and associated autoimmune conditions may be seen. Type II gastric NETs, comprising around 5-10%, develop from ECL cells in response to constitutively high gastrin levels from a gastrinoma, and are associated with ZES (85). Both type I and II gastric NETs are multifocal and primarily arise in the corpus (85).…”

“…Type II gastric NETs, comprising around 5-10%, develop from ECL cells in response to constitutively high gastrin levels from a gastrinoma, and are associated with ZES (85). Both type I and II gastric NETs are multifocal and primarily arise in the corpus (85). Type III gastric carcinoids, which are sporadic and solitary, represent approximately 10-15% of (74).…”

Revisión de tema: tumores neuroendocrinos gástricos.

“…La gastrina se une a los receptores de colecistoquinina B los cuales se encuentran en las células similares a las enterocromafines (ECL); esta unión estimula la secreción de la histamina por las células ECL. La histamina vía receptores H2 propicia la liberación de ácido por las células parietales (1) .…”

“…En situaciones de hipo o acloridia se produce la hiperplasia de células G llevando a la hipergastrinemia. La hipergastrinemia estimula crónicamente las células ECL, dando como resultado la hiperplasia de estas células y posteriormente la transformación hacia las neoplasias neuroendocrinas (1) . Desde el punto de vista genético el hallazgo más relevante es la pérdida de heterozigocidad en el locus del gen MEN-1 (11q13, menin), que ocurre en todos los pacientes con los TNEG tipo 2, en un 17-73% de los tipo 1 y un 25-50% de los tipo 3 (2) .…”