Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms

Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of malignancies that originate from the diffuse neuroendocrine cell system of the pancreas and gastrointestinal tract and have increasingly increased in number over the decades. GEP-NENs are roughly classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas; it is essential to understand the pathological classification according to the mitotic count and Ki67 proliferation index. In addition, with the advent of molecular-targeted drugs and somatostatin analogs and advances in endoscopic and surgical treatments, the multidisciplinary treatment of GEP-NENs has made great progress. In the management of GEP-NENs, accurate diagnosis is key for the proper selection among these diversified treatment methods. The evaluation of hormone-producing ability, diagnostic imaging, and histological diagnosis is central. Advances in the study of the genetic landscape have led to deeper understanding of tumor biology; it has also become possible to identify druggable mutations and predict therapeutic effects. Liquid biopsy, based on blood mRNA expression for GEP-NENs, has been developed, and is useful not only for early detection but also for assessing minimal residual disease after surgery and prediction of therapeutic effects. This review outlines the updates and future prospects of the epidemiology, diagnosis, and management of GEP-NENs.

Keywords: biomarkers; carcinoid tumor; gastroenteropancreatic neuroendocrine tumor; genetics.

Figure 1

Distribution of the primary sites of NENs. Numbers shown in parentheses denote the study samples in each reference. USA: United States of America. Data for the figure is based on references [12,16,17,18,21,22,23,27].

Figure 2

Mutation frequencies in neuroendocrine neoplasms arising from the gastrointestinal tract and pancreas. The percentages of samples mutated in individual tumor types are shown. PANET: Pancreatic neuroendocrine tumor, SBWDNET: Small bowel well-differentiated neuroendocrine tumor, RWDNET: Well-differentiated neuroendocrine tumor of the rectum, AWDNET: Well-differentiated neuroendocrine tumor of the appendix, HGNEC: High-grade neuroendocrine carcinoma of the colon and rectum.

Figure 3

Frequency of actionable genetic mutations in gastroenteropancreatic neuroendocrine neoplasms. Percentages of samples mutated in individual tumor types are shown. PANET: Pancreatic neuroendocrine tumor, SBWDNET: Small bowel well-differentiated neuroendocrine tumor, RWDNET: Well-differentiated neuroendocrine tumor of the rectum, AWDNET: Well-differentiated neuroendocrine tumor of the appendix, HGNEC: High-grade neuroendocrine carcinoma of the colon and rectum.