scholarly journals Multiple Endocrine Neoplasia Type 1 (MEN1): Loss of One MEN1 Allele in Tumors and Monohormonal Endocrine Cell Clusters But Not in Islet Hyperplasia of the Pancreas

2007 ◽  
Vol 92 (3) ◽  
pp. 1118-1128 ◽  
Author(s):  
Aurel Perren ◽  
Martin Anlauf ◽  
Tobias Henopp ◽  
Thomas Rudolph ◽  
Anja Schmitt ◽  
...  
Keyword(s):  
Endocrine Cell ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Endocrine Tumors ◽  
Cell Clusters ◽  
Endocrine Neoplasia ◽  
Islet Hyperplasia ◽  
Endocrine Neoplasia Type ◽  
Pancreatic Endocrine Tumors

Abstract Context: The occurrence of multiple small pancreatic endocrine tumors in patients suffering from multiple endocrine neoplasia type 1 (MEN1) represents a unique possibility to study early neoplasms and their potential precursor lesions. To date, it is unknown whether small islet-like endocrine cell clusters found in MEN1 patients are neoplastic or rather hyperplastic. It is also unclear whether microadenomas develop from islets. Design: We hypothesized that monohormonal endocrine cell clusters observed in MEN1 patients are small neoplasms with loss of heterozygosity of the MEN1 locus. Using a technique combining fluorescence in situ hybridization of the MEN1 locus and the centromeric region of chromosome 11q with hormone immunostaining, we examined resection specimens from four MEN1 patients. We focused our investigations on the following: 1) typical microadenomas; 2) monohormonal endocrine cell clusters; 3) endocrine and exocrine structures entrapped in microadenomas; and 4) morphologically normal islets. Results: Loss of one MEN1 allele was found in all 27 microadenomas and 19 of 20 (95%) monohormonal endocrine cell clusters. By contrast, it was absent in islets and ductal or acinar structures. Our results indicate that monohormonal endocrine cell clusters represent a minute form of microadenomas. Conclusion: The frequent presence of single nonneoplastic insulin cells in microadenomas and the occurrence of microadenomas in islets suggest an islet origin of microadenomas. Islet hyperplasia does not seem to be an obligatory stage in pancreatic MEN1-associated tumor development.

scholarly journals Surgery for Gastrinoma and Insulinoma in Multiple Endocrine Neoplasia Type 1

2006 ◽  
Vol 4 (2) ◽  
pp. 148-153 ◽  
Author(s):  
Jeffrey A. Norton ◽  
Tony D. Fang ◽  
Robert T. Jensen
Keyword(s):  
Gastric Acid ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Endocrine Tumors ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Pancreatic Endocrine Tumors ◽  
Gastric Acid Hypersecretion ◽  
Acid Hypersecretion

The surgical management of pancreatic endocrine tumors in patients with multiple endocrine neoplasia type 1 remains controversial. Gastrinoma and insulinoma are the 2 most common functional pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. Gastrinomas cause gastric acid hypersecretion and peptic ulcer disease that are best managed using proton pump inhibitors. Surgery to remove the gastrinoma in patients with multiple endocrine neoplasia type 1 is seldom curative unless a more extensive Whipple pancreaticoduodenectomy is performed. Because the prognosis is excellent, aggressive resections such as a Whipple procedure are only indicated for large, locally metastatic, advanced tumors. Furthermore, surgery to remove imageable tumors that are 2 cm in diameter is associated with excellent outcomes and decreased probability of liver metastases. Because gastrinomas are commonly multiple and most originate in the duodenum and develop lymph node metastases, the duodenum should be opened and all tumors and lymph nodes excised. Insulinomas cause hypoglycemia that results in neuroglycopenic symptoms. Medical management of the hypoglycemia is less effective than that of the gastric acid hypersecretion. Fortunately, the insulinoma is usually clearly identified using routine pancreatic imaging studies. There is a high likelihood of cure when the insulinoma is excised surgically. However, recurrent hypoglycemia may occur, and careful follow-up is indicated.

Management of Pancreatic Endocrine Tumors in Multiple Endocrine Neoplasia Type 1

2006 ◽  
Vol 30 (5) ◽  
pp. 643-653 ◽  
Author(s):  
Maria A. Kouvaraki ◽  
Suzanne E. Shapiro ◽  
Gilbert J. Cote ◽  
Jeffrey E. Lee ◽  
James C. Yao ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Endocrine Tumors ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Pancreatic Endocrine Tumors

scholarly journals Germline MEN1 mutations in sixteen Japanese families with multiple endocrine neoplasia type 1 (MEN1)

1999 ◽  
pp. 475-480 ◽  
Author(s):  
N Hai ◽  
N Aoki ◽  
A Matsuda ◽  
T Mori ◽  
S Kosugi
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Family Members ◽  
Premature Stop Codon ◽  
Germline Mutations ◽  
Endocrine Tumors ◽  
Men1 Gene ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is a syndrome of endocrine tumors involving the parathyroids, anterior pituitary and enteropancreatic neuroendocrine tissues, and is inherited in an autosomal dominant manner. Recently, the gene responsible for this syndrome, MEN1, was positionally cloned in 11q13. We aimed to assess the significance of MEN1 gene diagnostics in families with MEN1. DESIGN: Sixteen probands of familial MEN1 and their 40 family members were subjected to the study. METHODS: Full-length sequencing of the open reading frame and exon-intron boundaries in the MEN1 gene was performed with probands of familial MEN1. Family members were examined for the identified mutation in the proband. RESULTS: We identified heterozygous germline mutations of the MEN1 gene in all of 16 Japanese MEN1 families examined, achieving the highest detectability of MEN1 mutations in familial MEN1 among studies that examined more than 10 families. Eleven kinds of the identified MEN1 germline mutations were novel. More than half were nonsense or frameshift mutations resulting in a premature stop codon (9/15; 60%), and no mutation hot spots or no apparent genotype-phenotype relationships were observed, in support of the results of other studies. We identified 40 mutant MEN1 gene carriers and 16 non-carriers in the course of the present study in those families. CONCLUSIONS: Analysis of the germline mutations in the MEN1 gene, providing significantly useful clinical information to probands and family members of MEN1, should be considered as a standard procedure and categorized as belonging to Group 1 cancer predisposition testing by the American Society of Clinical Oncology.

scholarly journals Multiple Endocrine Neoplasia Type 1: Latest Insights

2020 ◽  
Author(s):  
Maria Luisa Brandi ◽  
Sunita K Agarwal ◽  
Nancy D Perrier ◽  
Kate E Lines ◽  
Gerlof D Valk ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Genetic Diagnosis ◽  
Diagnostic Tools ◽  
Surgical Approaches ◽  
Endocrine Tumors ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Basic Biology

Abstract Multiple Endocrine Neoplasia Type 1 (MEN1), a rare tumor syndrome that is inherited in an autosomal dominant pattern, is continuing to raise great interest for endocrinology, gastroenterology, surgery, radiology, genetics and molecular biology specialists. There have been two major clinical practice guidance papers that were published in the past two decades, with the most recent publication 8 years ago. Since then, several new insights on the basic biology and clinical features of MEN1 have appeared in the literature and those data are discussed in this review. The genetic and molecular interactions of the MEN1 encoded protein menin with transcription factors and chromatin modifying proteins in cell signaling pathways mediated by TGF-β/BMP, few nuclear receptors, Wnt/β-catenin and Hedgehog (Hh), and preclinical studies in mouse models have facilitated the understanding of the pathogenesis of MEN1-associated tumors and potential pharmacological interventions. The advancements in genetic diagnosis have offered a chance to recognize MEN1 related conditions in germline MEN1 mutation negative patients. There is a rapidly accumulating knowledge about clinical presentation in children, adolescents and pregnancy that is translatable into the management of these very fragile patients. The discoveries about the genetic and molecular signatures of sporadic neuro-endocrine tumors support the development of clinical trials with novel targeted therapies, along with advancements in diagnostic tools and surgical approaches. Finally, quality of life studies in patients affected by MEN1 and related conditions represent an effort necessary to develop a pharmacoeconomic interpretation of the problem. Because advances are being made both broadly and in focused areas, this timely review presents and discusses those studies collectively.

Presentation and Outcome of Pancreaticoduodenal Endocrine Tumors in Multiple Endocrine Neoplasia Type 1 Syndrome

2011 ◽  
Vol 94 (1) ◽  
pp. 58-65 ◽  
Author(s):  
Maria Vittoria Davì ◽  
Letizia Boninsegna ◽  
Luca Dalle Carbonare ◽  
Marco Toaiari ◽  
Paola Capelli ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Endocrine Tumors ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

scholarly journals The multiple endocrine neoplasia type 1 gene product, menin, inhibits the human prolactin promoter activity

2002 ◽  
Vol 29 (3) ◽  
pp. 297-304 ◽  
Author(s):  
H Namihira ◽  
M Sato ◽  
K Murao ◽  
WM Cao ◽  
S Matsubara ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Promoter Activity ◽  
Multiple Endocrine Neoplasia Type ◽  
Gh3 Cells ◽  
Endocrine Tumors ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Rat Pituitary ◽  
Human Prolactin

Menin is a protein encoded by the gene mutated in multiple endocrine neoplasia type 1 (MEN1) characterized by multiple endocrine tumors of the parathyroid glands, pancreatic islets and the anterior pituitary, especially prolactinoma. In this study, we examined the effects of menin on human prolactin (hPRL) expression. In rat pituitary GH3 cells stably expressing menin, both PRL gene expression/secretion and thymidine incorporation into DNA were inhibited as compared with mock-transfected cells. The transcriptional activity of PRL promoter in GH3 cells co-transfected with menin was significantly decreased. A deletion mutation (569 delC), which we identified in a Japanese MEN1 family, was introduced into menin. When GH3 cells were transfected with a mutant menin expression vector, inhibition of hPRL promoter activity was partially reversed. These observations suggest that menin inhibits hPRL promoter activity and cell proliferation, raising the possibility that menin might play an important role in the tumorigenesis of prolactinoma.

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