MicroRNA Signatures as Novel Biomarkers in Small Intestine Neuroendocrine Tumors Abstract #355

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#20 Paraneoplastic antigen Ma2 (PNMA2) auto-antibodies as biomarkers for early small intestine neuroendocrine tumors detection
Introduction: Small intestine neuroendocrine tumors (NETs) comprise well-differentiated NET (benign carcinoid), well-differentiated neuroendocrine carcinoma (malignant carcinoid) and poorly differentiated neuroendocrine carcinoma (NEC). The majority of NET patients have developed liver metastases at the time of diagnosis and surgery is then seldom curative. Novel predictive, diagnostic and prognostic markers are thus needed to improve our capabilities to diagnose and cure these tumors. We have previously identified six novel marker genes for neuroendocrine tumor cells by using Affymetrix microarrays and advanced bioinformatics. One of this markers, the paraneoplastic antigen Ma2 (PNMA2), which is normally expressed only in nervous tissue, can in the process of carcinogenesis be detected in tumors located outside the nervous system. The finding that Ma2 is expressed in small intestine neuroendocrine primary tumors and their metastases made it interesting to screen whether antibodies against Ma2 are present in the serum of NET patients.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: PhD Valeria Giandomenico
Authors: Cui T, Elgue G, Li S C, Hurtig M, ...
#47 Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in Patients with Neuroendocrine Tumors
Introduction: Carcinoid heart disease (CHD) is a known complication of neuroendocrine tumors (NETs), particularly of those arising from the small intestine, appendix and proximal colon (previously known as mid-gut carcinoids). CHD is characterized by right heart fibrotic lesions and has traditionally been defined by the degree of valvular involvement, most commonly in the form of tricuspid regurgitation. Right ventricular (RV) dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2) is upregulated in many fibrotic disorders. Increased tumor expression of CCN2 has been shown in patients with small intestinal NETs associated with peritoneal fibrosis. At present, its role in carcinoid heart disease is unknown.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Dr. Deidi S Bergestuen
#62 Genome-wide DNA methylation profiling of pancreatic neuroendocrine tumors identifies distinct methylation profiles and differentially methylated gene promoter regions associated with low, medium and high grade tumors
Introduction: Integration of genetics and epigenetics has emerged as a powerful approach to studying cellular differentiation (Mikkelsen et al, 2009) and tumorigenesis (Shen et al, 2007). The study of DNA methylation is of particular importance in cancer, as causal involvement has been demonstrated and it is the most stable of all epigenetic modifications, making it a desirable marker for both early detection and treatment of tumors. Hypermethylation of CpG sites in gene promoter regions leads to decreased gene expression; if such a gene is a tumor suppressor, this leads to carcinogenesis. To date, there have been no studies of genome-wide DNA methylation profiling of NETs. This study sets out to determine the DNA methylation profiles of low, intermediate and high grade pancreatic NET liver metastases with the intention of identifying dysregulated biological pathways in the development of these tumors. A protocol for the analysis formalin-fixed paraffin embedded tissue (FFPE) has also been developed in order to study these tumors in significant numbers following this pilot study.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Dr Christina Thirlwell
#78 The diagnostic and prognostic value of elevated proGRP levels in well- and moderately differentiated neuroendocrine tumors
Introduction: Chromogranin A (CgA) is the most frequently used marker in well- (grade 1) and moderately (grade 2) differentiated NETs. Although CgA is a more sensitive marker than the 5-HIAA, which was widely used until the last decade, CgA has some limitations. False-positively elevated CgA may occur in renal impairment, atrophic gastritis and during treatment of proton-pump inhibitors. Progastrin-releasing peptide (proGRP) was recently reported as a promising tumor marker for small cell lung cancer. Limited data suggests that ProGRP may be a potential tumor marker in NE tumors.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Msc Catharina M Korse
#106 Gastroenteropancreatic neuroendocrine tumors: single institution clinicopathological study
Introduction: Neuroendocrine cells are widely distributed throughout the body, and neoplasms from these dispersed cells can arise at many sites. They are distinguished into two broad categories: 1) Tumors identified as small cell lung carcinomas with biology and natural history of a high-grade malignancy and characteristics of small cell undifferentiated or anaplastic appearance by light microscopy. The WHO categorizes these tumors as poorly-differentiated neuroendocrine carcinomas; 2) Well-defined neuroendocrine tumors (NETs) with variable, but most lyindolent biologic behavior and characteristic well-differentiated histologic features. The majority arise in the gastrointestinal tract and collectively they are referred as gastroenteropancreatic neuroendocrine tumors (GEP/NETs). They include carcinoid tumors, pancreatic islet cell tumors (gastrinoma, insulinoma, glucagonoma, VIPoma, somatostatinoma), paragangliomas, pheochromocytomas, and medullary thyroid carcinomas. The WHO classifies the GEP/NETs as well-differentiated NETs (carcinoid tumors) if they are noninvasive and have benign behavior or uncertain malignant potential. In contrast, GEP/NETs with characteristics of low-grade malignancy with invasion of the muscularis propria or beyond, or metastases, are characterized as well-differentiated neuroendocrine carcinomas (malignant carcinoids). Pancreatic islet cell tumors, whether functioning or not, are classified as well-differentiated NETs or well-differentiated neuroendocrine carcinomas, due to the (depending on) histologic characteristics. The WHO classification for gastroenteropancreatic NETs based on stage (ie size and presence of metastases) and grade (mitotic rate, perineural and lymphovascular invasion, Ki-67 proliferative index) categorizes them as well-differentiated NETs, e.g., carcinoid tumors, or as well-differentiated neuroendocrine carcinomas.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Dr Michael M. Vaslamatzis
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