Biomarkers in Small Intestine NETs and Carcinoid Heart Disease: A Comprehensive Review.

Leonidas Diamantopoulos,Markos Kalligeros,Christos Toumpanakis

doi:10.3390/biology10100950

Abstract

Simple SummaryNeuroendocrine tumors (NET), a heterogeneous group of tumors arising from neuroendocrine cells, often pose a diagnostic and therapeutic challenge for the clinician. Biomarkers can serve as a useful diagnostic, prognostic, and predictive tool in the management of these rare tumors. For years the field of NET biomarkers was mainly based on products se-creted by neuroendocrine tumor cells, however, during the last decade the development of nov-el multianalyte biomarkers has rapidly evolved the field. The aim of this review is to summa-rize the literature on the use and limitations of available NET biomarkers for the diagnosis and management of small intestine neuroendocrine tumors (SI-NETs) and carcinoid heart disease.Biomarkers remain a valuable tool for the diagnosis and management of Neuroendocrine tumors (NETs). Traditional monoanalyte biomarkers such as Chromogranin A (CgA) and 5-Hydrocyondoleacetic acid (5-HIAA) have been widely used for many years as diagnostic, predictive and prognostic biomarkers in the field of NETs. However, the clinical utility of these molecules often has limitations, mainly inherent to the heterogeneity of NETs and the fact that these tumors can often be non-secretory. The development of new molecular multianalyte biomarkers, especially the mRNA transcript based “NETest”, has rapidly evolve the field and gives the ability for a “liquid biopsy” which can reliably assess disease status in real time. In this review we discuss the use of established and novel biomarkers in the diagnosis and management of small intestine NETs and carcinoid heart disease.

Highlights

Neuroendocrine neoplasms (NENs) first described as “karzinoide” by Dr Oberndorfer in 1907 [1], comprise a family of heterogeneous tumors which can range from well differentiated neuroendocrine tumors (NETs) to poorly differentiated neuroendocrine carcinomas (NECs) [2]
Despite the undeniable importance of imaging and biomarkers, Small intestine NETs (SI-NETs) diagnosis can only be established with tissue biopsy and further tumor grading based on the combination of Ki-67 proliferative index with cell mitotic rate [11]
PubMed was searched using the terms “neuroendocrine tumor”, “neuroendocrine neoplasm”, “midgut”, “small intestine”, “small bowel”, “biomarkers”, “chromogranin A”, “5-Hydroxyindoleacetic Acid (5-HIAA)”, “NETest”, “carcinoid syndrome”, carcinoid heart disease” to identify articles in English referring to SI-NETs, carcinoid syndrome, carcinoid heart disease and their respective biomarkers

Summary

Introduction

Neuroendocrine neoplasms (NENs) first described as “karzinoide” by Dr Oberndorfer in 1907 [1], comprise a family of heterogeneous tumors which can range from well differentiated neuroendocrine tumors (NETs) to poorly differentiated neuroendocrine carcinomas (NECs) [2]. Given that the majority of these tumors have somatostatin receptors, functional imaging modalities such as PET/CT with gallium-68–labeled somatostatin analogs have dramatically improved the diagnostic sensitivity [10]. Biomarkers such as Chromogranin A (CgA) and 24-h urinary 5-Hydrocyondoleacetic acid (5-HIAA) have been widely used as SI-NETs diagnostic aids, with several limitations and suboptimal diagnostic accuracy [11]. Despite the undeniable importance of imaging and biomarkers, SI-NET diagnosis can only be established with tissue biopsy and further tumor grading based on the combination of Ki-67 proliferative index with cell mitotic rate [11]

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