Low Accuracy of Tumor Markers for Diagnosing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 Patients

Laat, Joanne M. de; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, A.R.M.M.; Dekkers, Olaf M.; Herder, Wouter W. de; Horst-Schrivers, Anouk N A van der; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

doi:10.1210/jc.2013-1800

Cited by 73 publications

(65 citation statements)

References 28 publications

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“…Nevertheless, the AUCs were all significantly lower (Z-statistic O4.5, P!0.0001) for these markers which further raises the issue as to their utility in NETs (Marotta et al 2012, de Laat et al 2013). The subject is further complicated by the existence of several commercially available and laboratory-developed assays that have been developed to measure putative single NET detection analytes.…”

Section: Discussionmentioning

confidence: 96%

“…Each of the ELISA single analytes, in contrast, had significantly lower AUCs (ranging from 0.56 to 0.67). In contrast, ROC AUC curves for commercially available CgA RIAs (CIS-Bio and EuroDiagnostica, considered more sensitive than ELISA) generally range from 0.48 to 0.76 (Marotta et al 2012, de Laat et al 2013, Tohmola et al 2013. In histopathologically confirmed NETs, using a processingindependent analysis method which is also radioimmunebased but not commercially available, the metrics range from 73-86% (sensitivity) and 86-91% (specificity) (Jensen et al 2013).…”

Section: Discussionmentioning

confidence: 99%

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A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

Modlin

Drozdov

Alaimo

et al. 2014

Endocrine-Related Cancer

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A critical requirement in neuroendocrine tumor (NET) management is a sensitive, specific and reproducible blood biomarker test. We evaluated a PCR-based 51 transcript signature (NETest) and compared it to chromogranin A (CgA), pancreastatin (PST) and neurokinin A (NKA). The multigene signature was evaluated in two groups: i) a validation set of 40 NETs and controls and ii) a prospectively collected group of NETs (nZ41, 61% small intestinal, 50% metastatic, 44% currently treated and 41 age-sex matched controls). Samples were analyzed by a two-step PCR (51 marker genes) protocol and ELISAs for CgA, PST and NKA. Sensitivity comparisons included c 2 , non-parametric measurements, ROC curves and predictive feature importance (PFAI) analyses. NETest identified 38 of 41 NETs. Performance metrics were: sensitivity 92.8%, specificity 92.8%, positive predictive value 92.8% and negative predictive value 92.8%. Single analyte ELISA metrics were: CgA 76, 59, 65, and 71%; PST 63, 56, 59, and 61% and NKA 39, 93, 84, and 60%. The AUCs (ROC analysis) were: NETest: 0.96G0.025, CgA: 0.67G0.06, PST 0.56G0.06, NKA: 0.66G0.06. NETest significantly outperformed single analyte tests (area differences: 0.284-0.403, Z-statistic 4.85-5.9, P!0.0001). PFAI analysis determined NETest had most value (69%) in diagnosis (CgA (13%), PST (9%), and NKA (9%)). Test data were consistent with the validation set (NETest O95% sensitivity and specificity, AUC Z0.98 vs single analytes: 59-67% sensitivity, AUCs: 0.58-0.63). The NETest is significantly more sensitive and efficient (O93%) than single analyte assays (CgA, PST or NKA) in NET diagnosis. Blood-based multigene analytic measurement will facilitate early detection of disease recurrence and can predict therapeutic efficacy.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

Modlin

Drozdov

Alaimo

et al. 2014

Endocrine-Related Cancer

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“…In MEN1 patients, however, this finding could not be confirmed. de Laat et al (2013), for example, determined for the markers chromogranin A, PP and glucagon, a sensitivity of 45% and specificity of 75% for MEN1-associated pNENs. In their study, the diagnostic accuracy of these tumor markers was low compared to imaging (de Laat et al 2013).…”

Section: Tumor Markersmentioning

confidence: 99%

“…de Laat et al (2013), for example, determined for the markers chromogranin A, PP and glucagon, a sensitivity of 45% and specificity of 75% for MEN1-associated pNENs. In their study, the diagnostic accuracy of these tumor markers was low compared to imaging (de Laat et al 2013). These results were supported by several other studies (Granberg et al 1999, Walter et al 2012, Rehfeld et al 2014.…”

Section: Tumor Markersmentioning

confidence: 99%

The future: diagnostic and imaging advances in MEN1 therapeutic approaches and management strategies

Manoharan¹,

Albers²,

Bartsch³

2017

Endocrine-Related Cancer

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Prospective randomized data are lacking, but current clinical expert guidelines recommend annual screening examinations, including laboratory assessments and various imaging modalities (e.g. CT, MRI, scintigraphy and EUS) for patients with multiple endocrine neoplasia type 1 (MEN1). Routine screening is proposed to detect and localize neuroendocrine manifestations as early as possible. The goal is timely intervention to improve quality of life and to increase life expectancy by preventing the development of life-threatening hormonal syndromes and/or metastatic disease. In recent years, some studies compared different and new imaging methods regarding their sensitivity and utility in MEN1 patients. This present article reviews the proposed diagnostic tools for MEN1 screening as well as potential future perspectives.

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“…Pancreatic polypeptide " For pancreatic NETs, pancreatic polypeptide may be useful for the early detection of NETs of pancreatic origin in the context of MEN-1, although this is controversial because of its low sensitivity (41). In the absence of a clinical syndrome, serum tests for an extensive set of hormones are not indicated in nonfunctioning pNETs.…”

Section: Specific Biomarkersmentioning

confidence: 99%

GEP-NETs UPDATE: Secreting gastro-enteropancreatic neuroendocrine tumours and biomarkers

Verbeek¹,

Korse²,

Tesselaar

2016

European Journal of Endocrinology

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Neuroendocrine tumours (NETs) are rare tumours with an annual incidence in the population in a range of 2-5 new cases per 100 000 inhabitants. NETs are widely variable in terms of anatomical location, hormone production, clinical behaviour and syndromes they can cause. This article reviews the many localizations and clinical presentations of NETs with a main focus on clinical biomarkers and their use in medical practice.

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Low Accuracy of Tumor Markers for Diagnosing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 Patients

Abstract: The diagnostic accuracy of the tumor markers CgA, PP, and glucagon for pNET in MEN1 is low.

Cited by 73 publications

References 28 publications

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

The future: diagnostic and imaging advances in MEN1 therapeutic approaches and management strategies

GEP-NETs UPDATE: Secreting gastro-enteropancreatic neuroendocrine tumours and biomarkers

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