Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions
- 1 May 2007
- Vol. 56 (5), 637-644
- https://doi.org/10.1136/gut.2006.108910
Abstract
Background: Patients with a multiple endocrine neoplasia type 1 (MEN1)-associated Zollinger–Ellison syndrome (ZES) show multifocal duodenal gastrinomas and precursor lesions. Aims: To test these lesions for loss of heterozygosity (LOH) of the MEN1 gene locus on chromosome 11q13, and to investigate whether the MEN1-related endocrine cell changes also involved somatostatin cells. Material and methods: Tissue specimens from six patients with MEN1 and ZES were analysed by immunohistochemistry and immunofluorescence. LOH analysis was performed by fluorescence in situ hybridisation (FISH), using probes containing the MEN1 gene locus and the centromere 11 (C11) region. For simultaneous analysis of hormones and allelic deletions, a combined FISH/immunofluorescence protocol was established. Results: 28 of a total of 33 duodenal neuroendocrine tumours (NETs) were gastrin-producing tumours; 13/28 (46.4%) revealed LOH on 11q13 and/or C11. Five of the NETs were somatostatin-expressing tumours, two revealing LOH. Allelic loss was detected in tumours as small as 300 μm (gastrin) and 400 μm (somatostatin) in diameter. The gastrin-producing tumours showed different deletion/retention patterns. Hyperplastic somatostatin cell lesions, similar to those of the gastrin cells, were present in all patients. The hyperplastic lesions of both cell lines consistently retained both 11q13 alleles. Conclusions: Allelic deletion of the MEN1 gene may reflect a pivotal event in the development of multifocal gastrin and somatostatin cell neoplasms in the duodenum of patients with MEN1. The observation of distinct deletion patterns in small synchronous tumours supports the concept that each gastrin-producing tumour in an individual MEN1 patient arises from an independent cell clone.Keywords
This publication has 29 references indexed in Scilit:
- Microadenomatosis of the Endocrine Pancreas in Patients With and Without the Multiple Endocrine Neoplasia Type 1 SyndromeThe American Journal of Surgical Pathology, 2006
- Precursor Lesions in Patients With Multiple Endocrine Neoplasia Type 1--Associated Duodenal GastrinomasGastroenterology, 2005
- Persistent Hyperinsulinemic Hypoglycemia in 15 Adults With Diffuse NesidioblastosisThe American Journal of Surgical Pathology, 2005
- Surgery to Cure the Zollinger–Ellison SyndromeNew England Journal of Medicine, 1999
- The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoidsGastroenterology, 1997
- Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic endocrine tumors.1997
- Loss of Heterozygosity at 11q13: Analysis of Pituitary Tumors, Lung Carcinoids, Lipomas, and Other Uncommon Tumors in Subjects with Familial Multiple Endocrine Neoplasia Type 1Journal of Clinical Endocrinology & Metabolism, 1997
- Positional Cloning of the Gene for Multiple Endocrine Neoplasia-Type 1Science, 1997
- Allelic deletions on chromosome 11q13 in multiple tumors from individual MEN1 patients.1996
- Immunohistochemical Study of 100 Pancreatic Tumors in 28 Patients with Multiple Endocrine Neoplasia, Type IThe American Journal of Surgical Pathology, 1996