Endocrine Abstracts

Neuroendocrine tumor cells express a diverse array of activating and inhibitory receptors. Each receptor transduces a signal via individual pathways which often interact or overlap. Common stimulatory receptor families include those for EGF/TGFα, FGF, IGF, PDGF, VEGF, and TGFβ. EGF receptor (Her 1) activation results in several signal transduction cascades including Ras/Raf, MAPK, AKT and JNK leading to DNA synthesis and cell proliferation. Activated MAPK signaling i...

Background: The NETest is a multi-gene assay comprising 51 circulating neuroendocrine tumor specific transcripts. The quotient of the 51-gene assay is based upon multi-algorithmic data analysis. Eight cancer hallmarks or ‘omes’ (apoptome, epigenome, growth factor signalome, metabolome, proliferome, plurome, secretome SSTRome) represent 29 genes. The NETest is an accurate diagnostic (>90%) but its prognostic utility has not been assessed. In this study, we describe ex...

Background: No effective blood biomarker exists to detect and clinically manage bronchopulmonary (BP) neuroendocrine tumors. We developed a blood-based 51 neuroendocrine tumor (NET)-specific transcript set to diagnose and monitor gastroenteropancreatic NETs. In this study, we examined whether the signature functioned in lung NETs. Thereafter, we examined performance metrics to assess clinical utility. The multianalyte gene signature accurately diagnosed the tumor and in additi...

Background: The diagnosis of neuroendocrine tumor disease has been tardy due to a lack of sensitive, noninvasive technology to facilitate identification. In the 1960’s, diagnosis required tumor tissue attained by surgery or biopsy. Identification was by histopathology and immunohistochemistry (1975). Acquisition of information was limited by the morbidity of invasive strategies, inability to reassess and interpretation was user-dependent with low kappa values. The introdu...

Introduction: Neuroendocrine tumors of GI tract are a heterogeneous group of rare neoplasms that secrete peptides and amines. These tumors are highly vascular and their vascularity reflects increased tumour related angiogenesis. Adenosine, a major regulator of angiogenesis, is released by enhanced degradation of ATP, during cellular stress, damage and hypoxia.Material and methods: The expression of adenosine receptors (AR) was investigated in two human n...

Background: Peptide receptor radionuclide therapy (PRRT) is based on tumor somatostatin receptor (SSR) overexpression to deliver targeted isotope therapy. Functional imaging of SSR expression (SRE) is used as a predictor of efficacy, but there is no method to objectively predict PRRT efficacy. We report the efficacy of Predictive Quotient Index (PQI) to predict the utility of PPRT. PQI is derived from circulating NET transcript analysis (NETest) integrated with the tu...

Background: Small-bowel neuroendocrine tumours (SB-NET) commonly metastasise despite most being low grade. The NET nomogram developed, estimates 5- and 10-year survival in SB-NET by allocating scores for 15 clinicopathological parameters. We comparatively evaluated the prognostic power of this nomogram, the WHO/ENETS grading and AJCC/UICC staging systems.Methods: Patients with histologically-confirmed SB-NET were identified from databases at two tertiary...

Background: Predicting and monitoring PRRT is based upon NET overexpression of somatostatin receptor (SSR) to deliver targeted isotope therapy. Imaging SSR expression is ~60% accurate as a predictor of efficacy. However, it and other imaging modalities e.g., CT/MRI, have utility for monitoring response. Specific blood NET gene expression (Positive Predictor Quotient- [PPQ]) is accurate in predicting PRRT response (93–97%, Bodei et al. EJNMMI 2018). The utility of NET tran...

Background: The efficacy of PRRT is based upon NET over expression of somatostatin receptor (SSR) to deliver targeted isotope therapy. SSR expression (Krenning scale) compared to Predictive Quotient Index (PQI) (circulating NET transcript analysis mathematically integrated with grade) indicates the latter is more accurate for predicting PRRT efficacy. We evaluated whether PQI was specifically predictive or was prognostic for PRRT compared to other therapeutic strategi...

Background: There is currently no effective blood biomarker for lung neuroendocrine neoplasia diagnosis and management. We describe the clinical utility of a 51 neuroendocrine-specific gene expression set in blood to diagnose bronchopulmonary neuroendocrine tumors (BPNETs) and define their clinical status.Methods: The discovery set included BPNETs (n=154) and controls (n=90), randomly assigned (1:1) to a test and validation set. Specifi...