Reduced MEN1 Gene Expression in Pulmonary Carcinoids Is Associated With Metastatic Disease Abstract #212

Introduction: Lung carcinoids are neuroendocrine tumors that can be classified as typical (TC) or atypical (AC) carcinoids. Previously, MEN-1 mutations and associated LOH of 11q13 have been implied in tumorigenesis.
Aim(s): To examine MEN-1 promotor hypermethylation and gene expression and their correlation with clinical outcome.
Materials and methods: We determined MEN-1 mRNA expression in 20 ACs and 31 TCs by quantitative RT-PCR (exon 2/3 boundaries). Furthermore, we analyzed genomic DNA from 25 ACs and 22 TCs for MEN-1 promotor hypermethylation by Methylation Specific PCR. Results were compared to controls (normal tissues and neuroendocrine cell lines) and correlated with clinical outcome.
Conference: 8th Annual ENETS Conference (2011)
Category: Basic
Presenting Author: MSc Dorian R.A. Swarts

To read results and conclusion, please login ...

Further abstracts you may be interested in

#18 Long-acting release octreotide induce complete response in type 1 gastric carcinoid tumors
Introduction: Gastric endocrine tumors (GET) are increasingly recognized due to expanding indications of upper gastrointestinal endoscopy. Often silent and benign, GET may also be aggressive when sporadic and may sometimes mimic the course of gastric adenocarcinoma. Current incidence of GETs is estimated at around 8% of digestive endocrine tumors. Yearly age-adjusted incidence is around 0.2 per population of 100,000. Gastric carcinoids (ECLomas) develop from gastric enterochromaffin-like cells (ECL cells) in response to chronically elevated gastrin. Type 1 tumors (ECLomas in the course of atrophic gastritis) may occur in conditions of achlorhydria secondary to auto-immune atrophic fundic gastritis. It occurs mostly in women and they are non-functioning tumors, typically found during upper GI endoscopy performed for dyspepsia. ECLomas present frequently as multiple polyps, usually < 1 cm in diameter in the gastric fundus. Type 1 tumors are almost exclusively benign lesions with little risk of deep invasion of the gastric parietal wall. The neoplastic ECL cells become progressively dedifferentiated with an increasing number of Ki-67 immunoreactive (IR) cell nuclei. In addition, there is a substantial decrease in argynophil and IR NE cells that can be visualized by conventional methods. ECLomas secondary to hypergastrinemia should be closely followed for signs of clinical and histopathological tumor progression. Such ECLomas deserve early, active, radical surgical treatment.
Traditionally, gastric carcinoid type 1 (GCA1s) are endoscopically or surgically removed, depending on the number, appearance and size of the tumors. Antrectomy, with surgical excision of the majority of the G cells, is thought to facilitate regression of these tumors by removing the source of excessive gastrin secretion; however, the long-term benefits of antrectomy still remain uncertain. Although proton pump inhibitors are effective in reducing hypergastrinemia-induced gastric acid hypersecretion in GCA2, they do not affect ECL-cell hyperplasia, and therefore their role in GCA1 is limited. Moreover, in selected cases, significant reduction of hypergastrinemia does not prevent development of ECL carcinoid, suggesting that, in addition to hypergastrinemia, other pathogenic or genetic factors may be involved. Treatment with somatostatin analogues (SSA) might impede ECL-cell hyperplasia by suppressing gastrin secretion and/or by a direct anti-proliferative effect on ECL cells. Treatment with SSAs in GCA1 leads to a substantial tumor load reduction, with a concomitant decrease of serum gastrin levels. Published data indicate an important anti-proliferative effect of SSA on ECL cells, providing clinical benefit and obviating, at least temporarily, the need for invasive therapies for GCA1. Morphometric studies demonstrated that, while antrectomy specifically decreased the volume of ECL cells versus the total volume of endocrine cells, octreotide reduces the overall endocrine cell volume. Although the number of treated patients is small, it has been suggested that SSA may exert important anti-proliferative effects either directly, by inhibiting ECL-cells proliferation, or indirectly through suppression of gastrin hypersecretion.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: MD Ricardo Caponero
#58 Surgical approaches in 84 patients with insulinomas in multiple endocrine neoplasia type 1 (MEN 1)
Introduction: Management of insulinomas in the setting of Multiple Endocrine Neoplasia type 1 (MEN1) remains controversial.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Dr Delphine Vezzosi
#83 Surgical treatment of duodenopancreatic neuroendocrine tumors (pNETs) in patients with multiple endocrine neoplasia type 1 (MEN 1): a Dutch consensus statement
Introduction: Duodenopancreatic neuroendocrine tumors (pNETs) in multiple endocrine neoplasia type 1 (MEN 1) are the most important cause of MEN 1-related death. Surgery is the only curative treatment, but controversy exists on the optimal strategy. Recent guidelines on pNETs have limited recommendations specific for MEN 1. Therefore, a Dutch multidisciplinary consensus meeting was organized.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: MD Carolina RC Pieterman
#102 Presentation and outcome of pancreaticoduodenal tumors in Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome
Introduction: Multiple endocrine neoplasia type 1 (MEN 1) is a rare autosomal dominant condition characterized by the development of parathyroid, pancreaticoduodenal endocrine and pituitaty tumors. Pancreaticduodenal endocrine tumors (PDETs) are a frequent manifestation of MEN 1, with a prevalence ranging from 30 to 75%, and represent a major cause of death in one-third of patients. There is continuing debate on their management, mainly on the optimal surgical strategy, due to their multicentricity and high recurrence rate.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: MD Maria Vittoria Davi'
#120 Somatostatin receptors 1-5 expression in a large series of well-differentiated neuroendocrine tumors
Introduction: For their antisecretive and antiproliferative effect somatostatin analogs (SA) have been used in the treatment of neuroendocrine tumors (NETs), based on the expression of somatostatin receptors (sstRs). The potential availability of new SA for the treatment of patients with NETs suggests a better characterization of sstRs.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Dr Paola Loli