Investigation of the utility of current and novel neuroendocrine tumour markers

Abstract

Neuroendocrine neoplasms (NENs) arise from cells within the diffuse neuroendocrine system. Five year survival may be as low as 30%. Chromogranin A (Cg A) is the best available NEN biomarker. Lack of standardisation between Cg A assays, makes direct comparison between them difficult. Comparison of diagnostic accuracy between four commonly used Cg A assays showed there was no significant difference in diagnostic accuracy when investigating NEN patients with/without liver metastases. Concordance between assays was variable and this was further examined to establish whether assays in combination may improve diagnostic accuracy. Cisbio and SAS were the least concordant and this combination was the most useful in predicting a NEN diagnosis. Calcitonin is the most sensitive and specific biomarker for medullary thyroid carcinoma. The study established local reference ranges for the new Diasorin® calcitonin assay and demonstrated that reference ranges quoted by the manufacturers would lead to increase in false positive results in the local population. Further, this study confirmed that the manufacturers’ recommendation to use diagnostic cut-offs established using the old Cisbio assay for this new assay needed revision. Thus, despite standardisation of antisera specificities, diagnostic cut-offs from one assay cannot be automatically extrapolated to another. None of the existing biomarkers fit the paradigm of a definitive NEN marker and hence the need for novel biomarkers. Circulating Cocaine and Amphetamine Regulated Transcript (CART) levels are elevated in NEN patients. This study demonstrated that circulating CART was increased in all types of NEN, particularly pancreatic NENs. While CART was expressed in all phaeochromocytoma tissues, expression in other NENs was variable. In addition to being a diagnostic marker, CART may also be a prognostic indicator as levels are higher in patients with progressive disease. Further long-term longitudinal studies are needed to fully assess the role of CART as a diagnostic and prognostic marker for NEN.