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Biology
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Biomarkers in Neuroendocrine Tumors
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Biomarkers in Neuroendocrine Tumors

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Medical Biology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 13387

Special Issue Editor

Dr. Apostolos V. Tsolakis

E-Mail Website
Guest Editor
Karolinska Institute Department of Medicine, Huddinge, Sweden
Interests: neuroendocrine tumors; advanced therapeutic endoscopy

Special Issue Information

Dear Colleagues,

Neuroendocrine tumors (NETs) comprise a heterogeneous group of rare tumors with an increasing prevalence. As with any type of neoplasia, the identification of specific and sensitive biomarkers that can facilitate diagnosis, treatment, and follow-up is mandatory for NETs. Biomarkers are measurable in various types of biological media and can derive from cell surface, cytoplasma or be expressed in the nucleus. Due to the paucity of NETs, there is a lack of comprehensive knowledge of the existing respective biomarkers, their advantages, and limitations. This overview examines the clinical application of current NET biomarkers and even includes the possible use of novel ones.

Dr. Apostolos V. Tsolakis
Guest Editor

Manuscript Submission Information

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Keywords

  • biomarkers
  • neuroendocrine tumors

Published Papers (4 papers)

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Research

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13 pages, 1316 KiB  
Article
The Role of Serum 5-HIAA as a Predictor of Progression and an Alternative to 24-h Urine 5-HIAA in Well-Differentiated Neuroendocrine Neoplasms
by Maria Wedin, Sagar Mehta, Jenny Angerås-Kraftling, Göran Wallin and Kosmas Daskalakis
Biology 2021, 10(2), 76; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10020076 - 21 Jan 2021
Cited by 16 | Viewed by 2770
Abstract
Our aim was to investigate the clinical utility of serum 5HIAA for disease surveillance and diagnostic purposes in a cohort of patients with well-differentiated neuroendocrine neoplasms (WD-NENs). Forty-eight patients with WD-NENs and concurrent serum and urinary 5HIAA testing, as well as CT/MRI imaging, [...] Read more.
Our aim was to investigate the clinical utility of serum 5HIAA for disease surveillance and diagnostic purposes in a cohort of patients with well-differentiated neuroendocrine neoplasms (WD-NENs). Forty-eight patients with WD-NENs and concurrent serum and urinary 5HIAA testing, as well as CT/MRI imaging, were included. Analysis of matching-pairs did not reveal any association between RECIST 1.1 responses and changes in serum 5HIAA levels (p = 0.673). In addition, no correlation was evident between RECIST 1.1 responses and >10%, >25% or >50% changes in serum 5HIAA levels (Fisher’s exact test p = 0.380, p > 0.999, and p > 0.999, respectively). The presence of liver metastases and extensive liver tumor involvement were associated with higher serum 5HIAA levels (p = 0.045 and p = 0.041, respectively). We also confirmed a strong linear correlation between the measurements of serum and urine 5HIAA (n = 24, r = 0.791, p < 0.0001). The concordance rate of serum and urinary 5HIAA positivity at standardized laboratory cut-offs was 75%. In patients with normal renal function tests, the concordance between the two methods was as high as 89%, and a sensitivity and specificity of 80% and 88.9%, respectively, was evident (Cohen’s kappa coefficient = 0.685). In conclusion, serum 5HIAA performs well compared to urinary testing for diagnostic purposes, mainly in advanced disease stages, and corresponds well to liver tumor burden. However, it is not adequate to predict tumor progression. Full article
(This article belongs to the Special Issue Biomarkers in Neuroendocrine Tumors)
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Review

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13 pages, 1107 KiB  
Review
Biomarkers in Small Intestine NETs and Carcinoid Heart Disease: A Comprehensive Review
by Markos Kalligeros, Leonidas Diamantopoulos and Christos Toumpanakis
Biology 2021, 10(10), 950; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10100950 - 23 Sep 2021
Cited by 6 | Viewed by 3279
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Biomarkers in Neuroendocrine Tumors)
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14 pages, 352 KiB  
Review
A Critical Appraisal of Contemporary and Novel Biomarkers in Pheochromocytomas and Adrenocortical Tumors
by Marina Tsoli, Kosmas Daskalakis, Eva Kassi, Gregory Kaltsas and Apostolos V. Tsolakis
Biology 2021, 10(7), 580; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10070580 - 25 Jun 2021
Cited by 4 | Viewed by 2162
Abstract
Pheochromocytomas/Paragangliomas (PPGLs) and adrenocortical tumors are rare neoplasms with significant heterogeneity in their biologic and clinical behavior. Current diagnostic and predictive biomarkers include hormone secretion, as well as histopathological and genetic features. PPGL diagnosis is based on biochemical measurement of catecholamines/metanephrines, while histopathological [...] Read more.
Pheochromocytomas/Paragangliomas (PPGLs) and adrenocortical tumors are rare neoplasms with significant heterogeneity in their biologic and clinical behavior. Current diagnostic and predictive biomarkers include hormone secretion, as well as histopathological and genetic features. PPGL diagnosis is based on biochemical measurement of catecholamines/metanephrines, while histopathological scoring systems have been proposed to predict the risk of malignancy. Adrenocortical tumors are mostly benign, but some can be malignant. Currently, the stage of disease at diagnosis and tumor grade, appear to be the most powerful prognostic factors. However, recent genomic and proteomic studies have identified new genetic and circulating biomarkers, including genes, immunohistochemical markers and micro-RNAs that display high specificity and sensitivity as diagnostic or prognostic tools. In addition, new molecular classifications have been proposed that divide adrenal tumors in distinct subgroups with different clinical outcomes. Full article
(This article belongs to the Special Issue Biomarkers in Neuroendocrine Tumors)

Other

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10 pages, 2185 KiB  
Commentary
Second-Generation Neuroendocrine Immunohistochemical Markers: Reflections from Clinical Implementation
by Carl Christofer Juhlin
Biology 2021, 10(9), 874; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10090874 - 05 Sep 2021
Cited by 14 | Viewed by 4375
Abstract
When analyzing tumors by histopathology, endocrine pathologists have traditionally been restricted to a few key immunohistochemical markers related to secretory vesicles in order to pinpoint neuroendocrine differentiation—most notably Chromogranin A (CGA) and Synaptophysin (SYP). Although proven of great clinical utility, these markers sometimes [...] Read more.
When analyzing tumors by histopathology, endocrine pathologists have traditionally been restricted to a few key immunohistochemical markers related to secretory vesicles in order to pinpoint neuroendocrine differentiation—most notably Chromogranin A (CGA) and Synaptophysin (SYP). Although proven of great clinical utility, these markers sometimes exhibit tissue-specific patterns depending on tumor origin, and non-neuroendocrine tumors might sometimes display focal expression. Moreover, CGA and SYP might be partially or totally absent in highly proliferative neuroendocrine carcinomas, making the diagnosis particularly challenging on small biopsies of metastatic lesions with unknown location of the primary tumor. The advent of second-generation neuroendocrine markers ISL LIM Homeobox 1 (ISL1), INSM Transcriptional Repressor 1 (INSM1) and Secretagogin (SECG) have expanded the pathology toolbox considerably, constituting markers that often retain expression even in poorly differentiated neuroendocrine carcinomas. As non-neuroendocrine tumors seldom express these antigens, the specificity of ISL1, INSM1 and SECG make them welcome additions to clinical practice. In this commentary, recent advances of this field as well as initial clinical experiences from a tertiary neuroendocrine center are discussed. Full article
(This article belongs to the Special Issue Biomarkers in Neuroendocrine Tumors)
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