Pathogenesis of ECL cell tumors in humans.
In ECL cell tumors developed in the setting of hypergastrinemic conditions (ECL cell carcinoids type 1 and 2), hypergastrinemia is the dominant agent acting as a promoter in all steps (hyperplasia-dysplasia-neoplasia) of the tumorigenic sequence. In contrast, it apparently lacks transforming properties as shown by the absence of ECL cell carcinoids in patients exposed to hypergastrinemia alone, i.e., those with sporadic Zollinger-Ellison syndrome. The potential transforming factors include: the allelic loss of the MEN-1 suppressor gene in the genetically predisposed MEN-1 patients, an alteration that may induce ECL cell tumors even in the absence of hypergastrinemia; the still unknown factor(s) associated with atrophic corporal gastritis; agents whose role in the induction of human ECL cell tumors is still unclarified, such as basic Fibroblast Growth Factor, human Chorionic Gonadotropin-alpha and Transforming Growth Factor-alpha; and agents having a favoring role on the ECL exposure to mitogens such as BCL-2. No information is currently available on the pathogenesis of gastrin-independent, sporadic ECL cell carcinoids (type 3) or of gastric neuroendocrine carcinomas.
Bordi
C
C
Institute of Anatomic Pathology, University of Parma, Italy.
D'Adda
T
T
Azzoni
C
C
Ferraro
G
G
D000818:Animals; D002276:Carcinoid Tumor / Q000453:epidemiology / Q000473:pathology*; D019861:Enterochromaffin-like Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D016222:Fibroblast Growth Factor 2; D005755:Gastrins / Q000378:metabolism; D005757:Gastritis, Atrophic / Q000473:pathology; D015292:Glycoprotein Hormones, alpha Subunit / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012727:Sex Characteristics; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000473:pathology*
D005755:Gastrins; D015292:Glycoprotein Hormones, alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D016222:Fibroblast Growth Factor 2