scholarly journals Plasma acylated and plasma unacylated ghrelin: useful new biomarkers in patients with neuroendocrine tumors?

2016 ◽  
Vol 5 (4) ◽  
pp. 143-151 ◽  
Author(s):  
Roxanne C S van Adrichem ◽  
Aart Jan van der Lely ◽  
Martin Huisman ◽  
Piet Kramer ◽  
Richard A Feelders ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Tnm Classification ◽  
Venous Blood ◽  
Neuron Specific Enolase ◽  
Age At Diagnosis ◽  
Proliferation Index ◽  
Clinical Parameters ◽  
Unacylated Ghrelin ◽  
Fasting Plasma

To date, the value of fasting plasma acylated ghrelin (AG) and unacylated ghrelin (UAG) as potential novel biomarkers in patients with neuroendocrine tumors (NETs) is unknown. The aims of this study are to (i) compare fasting AG and UAG levels between nonobese, nondiabetic NET patients (N=28) and age- (±3 years) and sex-matched nonobese, nondiabetic controls (N=28); and (ii) study the relationship between AG, UAG, and AG/UAG ratios and biochemical (chromogranin-A (CgA) and neuron-specific enolase (NSE) levels) and clinical parameters (age at diagnosis, sex, primary tumor location, carcinoid syndrome, ENETS TNM classification, Ki-67 proliferation index, grading, prior incomplete surgery) in NET patients. Fasting venous blood samples (N=56) were collected and directly stabilized with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride after withdrawal. Plasma AG and UAG levels were determined by ELISA. Expression of ghrelin was examined in tumor tissue by immunohistochemistry. There were no significant differences between NET patients and controls in AG (median: 62.5 pg/mL, IQR: 33.1–112.8 vs median: 57.2pg/mL, IQR: 26.7–128.3, P=0.66) and UAG in levels (median: 76.6pg/mL, IQR: 35.23–121.7 vs median: 64.9, IQR: 27.5–93.1, P=0.44). No significant correlations were found between AG, UAG, and AG/UAG ratios versus biochemical and clinical parameters in NET patients with the exception of age at diagnosis (AG: ρ= −0.47, P=0.012; AG/UAG ratio: ρ= −0.50, P=0.007) and baseline chromogranin-A levels (AG/UAG ratio: ρ= −0.44, P=0.019). In our view, fasting plasma acylated and unacylated ghrelin appear to have no value as diagnostic biomarkers in the clinical follow-up of patients with NETs.

Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors

Cancer ◽  
1999 ◽  
Vol 86 (5) ◽  
pp. 858-865 ◽  
Author(s):  
Emilio Bajetta ◽  
Leonardo Ferrari ◽  
Antonia Martinetti ◽  
Luigi Celio ◽  
Giuseppe Procopio ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Carcinoembryonic Antigen ◽  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Neuron Specific Enolase

scholarly journals Chromogranin A, Ki-67 index and IGF-related genes in patients with neuroendocrine tumors

2013 ◽  
Vol 2 (4) ◽  
pp. 172-177 ◽  
Author(s):  
R C S van Adrichem ◽  
L J Hofland ◽  
R A Feelders ◽  
M C De Martino ◽  
P M van Koetsveld ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Insulin Receptors ◽  
Proliferation Index ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Igf Binding Proteins ◽  
Igf Receptors ◽  
Igf Binding

Chromogranin A (CgA) and the Ki-67 proliferation index are considered as important biochemical and pathological markers for clinical behaviour of gastroenteropancreatic neuroendocrine tumors (GEP NETs), respectively. The IGF system has been suggested as an important regulator of GEP NET proliferation and differentiation. A possible relationship between serum CgA (sCgA), Ki-67 proliferation index, and expression of IGF-related genes in patients with GEP NETs has not been demonstrated yet. This study investigates the relationship between sCgA, the Ki-67 proliferation index, and the expression of IGF-related genes in GEP NET tissues and their relation with 5-year survival. Tumor and blood samples from 22 GEP NET patients were studied. Tumoral mRNA expression of IGF-related genes (IGFs: IGF1, IGF2; IGF receptors: IGF1R, IGF2R; insulin receptors: subtype A (IR-A) and B (IR-B); IGF-binding proteins (IGFBPs): IGFBP1, IGFBP2, IGFBP3, and IGFBP6) was measured using quantitative RT-PCR. Ki-67 proliferation index was determined using immunohistochemistry. sCgA was measured with ELISA. Five-year survival in patients with nonelevated sCgA (n=11) was 91 vs 46% in patients with elevated sCgA (n=11) (P=0.006). IR-A mRNA expression was significantly higher in tumors obtained from patients with elevated sCgA than in those from patients with nonelevated sCgA (6.42±2.08 vs 2.60±0.40; P=0.04). This data suggests that sCgA correlates well with 5-year survival of GEP NET patients, and that IR-A mRNA expression correlates well with tumor mass in GEP NET patients.

scholarly journals Neuroendocrine Tumors — Laboratory Diagnosis

2010 ◽  
Vol 29 (4) ◽  
pp. 254-264 ◽  
Author(s):  
Anna Tzontcheva
Keyword(s):  
Gastrointestinal Tract ◽  
Tumor Markers ◽  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Endocrine Cells ◽  
Neuron Specific Enolase ◽  
Laboratory Diagnosis ◽  
Pancreatic Tumors ◽  
Endocrine Pancreatic Tumors ◽  
Well Differentiated

Neuroendocrine Tumors — Laboratory DiagnosisNeuroendocrine tumors (NETs) are a heterogeneous group of neoplasms originating from endocrine cells, which are characterized by the presence of secretory granules as well as the ability to produce biogenic amines and polypeptide hormones. These tumors originate from endocrine glands such as the adrenal medulla, the pituitary, and the parathyroids, as well as endocrine islets within the thyroid or the pancreas, and dispersed endocrine cells in the respiratory and gastrointestinal tract. The clinical behavior of NETs is extremely variable; they may be functioning or not functioning, ranging from very slow-growing tumors (well-differentiated NETs), which are the majority, to highly aggressive and very malignant tumors (poorly differentiated NETs). Classically, NETs of the gastrointestinal tract are classified into 2 main groups: (1) carcinoids and (2) endocrine pancreatic tumors (EPTs). Most neuroendocrine tumors produce and secrete a multitude of peptide hormones and amines. Some of these substances cause a specific clinical syndrome: carcinoid, Zollinger-Ellison, hyperglycemic, glucagonoma and WDHA syndrome. Specific markers for these syndromes are basal and/or stimulated levels of urinary 5-HIAA, serum or plasma gastrin, insulin, glucagon and vasoactive intestinal polypeptide, respectively. Some carcinoid tumors and about one third of endocrine pancreatic tumors do not present any clinical symptoms and are called ‘nonfunctioning’ tumors. Therefore, general tumor markers such as chromogranin A, pancreatic polypeptide, serum neuron-specific enolase and subunits of glycoprotein hormones have been used for screening purposes in patients without distinct clinical hormone-related symptoms. Among these general tumor markers chromogranin A, although its precise function is not yet established, has been shown to be a very sensitive and specific serum marker for various types of neuroendocrine tumors. This is because it may also be elevated in many cases of less well-differentiated tumors of neuroendocrine origin that do not secrete known hormones. At the moment, chromogranin A is considered the best general neuroendocrine serum or plasma marker available both for diagnosis and therapeutic evaluation, and is increased in 50-100% of patients with various neuroendocrine tumors. Chromogranin A serum or plasma levels reflect tumor load, and it may be an independent marker of prognosis in patients with midgut carcinoids.

scholarly journals Metastatic Non-Functional Pancreatic Neuroendocrine Tumor in a Patient With a Pathogenic TSC1 Mutation

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1000-A1000
Author(s):  
Aleksandra Sliwinska ◽  
David McFadden ◽  
Carl D Malchoff
Keyword(s):  
Ct Scan ◽  
Tuberous Sclerosis ◽  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Proliferation Index ◽  
Liver Mass ◽  
Pancreatic Lesion ◽  
Increased Risk ◽  
Pet Ct ◽  
History Of

Abstract Introduction: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder caused by mutations in two tumor suppressor genes (TSC1 and TSC2) encoding proteins critical in cell growth and proliferation and is associated with an increased risk for benign and malignant tumors. Pancreatic neuroendocrine tumors (PNET) occur in 1.5-1.8% of patients with TSC. They have been primarily reported in TSC2, with only a few cases in the context of TSC1. We describe a non-functional metastatic PNET in a patient with a known pathogenic TSC1 mutation. Case Description: A 49-year old female with a past medical history of bipolar disease, a family history of TSC1 in a daughter, a known pathologic TSC1 mutation (c.2356C>T), and previous history of renal cell carcinoma (RCC) was evaluated for a pancreatic lesion with likely liver metastases. Two years prior to the presentation, a 10 mm pancreatic lesion was initially noted on the CT scan during a renal mass evaluation. Nephrectomy confirmed the RCC. Two years later, surveillance imaging revealed two new lesions in the liver, and the pancreatic lesion had enlarged to 1.3 cm. She denied symptoms suggestive of a functional PNET, and her physical exam was unremarkable. Gallium-68 dotatate (GA-68) PET/CT scan demonstrated avid lesions of both the pancreatic tail and left hepatic lobe. Biopsy of the 3 cm liver mass revealed a metastatic high-grade neuroendocrine carcinoma (mib-1 proliferation index of 15%) favoring a primary PNET. Immunohistochemical stains were positive for chromogranin A, synaptophysin, EMA, PAX 8, CK 20, and villin. Stains for CA 19-9 and CK 7 were negative. Biochemical testing suggested that the PNET was non-functional. Specifically, serum concentrations of gastrin, somatostatin, glucagon, glucose, C-peptide, proinsulin, pancreatic polypeptide, chromogranin A, and vascular endothelial growth factor were within normal limits. The patient underwent distal pancreatectomy and resection of the liver mass. Pathological specimens confirmed the diagnosis of a PNET. The patient remained asymptomatic and was monitored regularly with MRI and GA-68 PET/CT scans without further evidence of the disease for 1.5 years. Conclusions: We conclude that this patient harboring a c.2356C>T TSC1 mutation developed a non-functional metastatic PNET. PNET is a likely component of TSC1. References: 1.Lodish, M. B., & Stratakis, C. A. (2010). Endocrine tumors in neurofibromatosis type 1, tuberous sclerosis, and related syndromes. Best practice & research Clinical endocrinology & metabolism, 24(3), 439-449.2.Dworakowska, D., & Grossman, A. B. (2009). Are neuroendocrine tumors a feature of tuberous sclerosis? A systematic review. Endocrine-Related Cancer, 16(1), 45.

scholarly journals Chromogranin-A as a Serum Marker for Neuroendocrine Tumors: Comparison with Neuron-Specific Enolase and Correlation with Immunohistochemical Findings

1999 ◽  
Vol 14 (3) ◽  
pp. 160-166 ◽  
Author(s):  
L. Giovanella ◽  
S. la Rosa ◽  
L. Ceriani ◽  
S. Uccella ◽  
P. Erba ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Secretory Granules ◽  
Neuron Specific Enolase ◽  
Serum Levels ◽  
Tissue Expression ◽  
Neuroendocrine Cells ◽  
Analytical Performance ◽  
Helical Computed Tomography ◽  
Tumor Extent

Background Chromogranin-A (Cg-A) is a 439-amino-acid protein contained in secretory granules of neuroendocrine cells, in addition to specific hormone peptides or neuropeptides. Since Cg-A is co-released with peptide hormones its serum concentration can be used as a marker of neuroendocrine tumors. Aim Evaluation of the analytical performance of a new IRMA method for Cg-A assay and of the clinical value of serum Cg-A and neuron-specific enolase (NSE) in neuroendocrine tumors. In addition, we compared the diagnostic usefulness of both Cg-A and NSE serum levels and their relationship to tissue expression. Patients and methods Initially we evaluated the analytical performance (intra- and interassay imprecision, dilution test and detection limit) of the Cg-A RIACT method (CIS Bio-International, Gifsur-Yvette, France). We selected 50 patients affected by various histologically confirmed neuroendocrine tumors (NETs): 111In-pentetreotide scan and helical computed tomography were employed to assess tumor extent. Cg-A and NSE were measured before surgery in serum samples of patients and 50 age-matched controls by IRMA methods. After surgery immunohistochemical stains for Cg-A and NSE were performed on surgical specimens of tumor tissue. Results Cg-A levels were significantly higher (p<0.0001) in patients with NETs than in healthy controls and we found a positive correlation between serum and tissue expression (p<0.05). Serum levels of Cg-A were also related to tumor extent (p<0.05) but in some cases we observed significant elevation of serum Cg-A in small, intensely immunoreactive NETs. ROC curve analysis showed better accuracy for serum Cg-A compared to NSE in the diagnosis of NETs, while no significant relationship was found between serum expression and immunostaining for NSE. Discussion Our results confirmed the biological and clinical significance of circulating Cg-A as an expression of granular content in neuroendocrine tissues and supported the complementary usefulness of serum Cg-A in the diagnosis and evaluation of NETs together with imaging modalities.

scholarly journals Clinical significance of Pro-Gastrin-Releasing Peptide, Neuron-Specific Enolase, Chromogranin A and Squamous Cell Cancer Antigen in pulmonary neuroendocrine tumors

2019 ◽  
Author(s):  
NURİ TUTAR ◽  
NUR ALEYNA YETKİN ◽  
CEVAT YAZICI ◽  
ÖMER ÖNAL ◽  
OLGUN KONTAŞ ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Neuroendocrine Tumors ◽  
Squamous Cell ◽  
Chromogranin A ◽  
Cell Cancer ◽  
Neuron Specific Enolase ◽  
Cell Lung Carcinoma ◽  
Study Results ◽  
Significant Difference ◽  
Nsclc Patients

Introduction It is not always easy to diagnose pulmonary neuroendocrine tumors (PNET).The aim of the present study is to make a differential diagnosis by studying the same markers in patients with non-small-cell lung carcinoma (NSCLC), patients with benign lung disease (chronic obstructive pulmonary disease and pneumonia) and healthy volunteers to determine the roles of these markers in pulmonary neuroendocrine tumors (PNET) diagnosis and to identify their power. Methods A total of 100 participants including 23 PNET patients and 28 NSCLC patients who were pathologically diagnosed but not yet treated, 25 participants with benign disease and 24 healthy volunteers were included in this cross-sectional study. Results No significant difference was found between the chromogranin A (CgA)and squamous cell carcinoma antigen 1 (SCCA1) values among the groups (PNET - NSCLC - Benign - Healthy volunteers)but the difference in progesterone-releasing peptide (Pro-GRP), neuron-specific enolase (NSE) and adjusted NSE was statistically significant (P values were respectively Pro-GRP p = 0.006, NSE p = 0.015, NSE adjusted p = 0.09).In a comparison of the PNET-NSCLC groups, having a Pro-GRP value higher than 84.6 pg / mL revealed PNET with 60.9% sensitivity and 89.3% specificity (p=0.001). Conclusion The Pro-GRP value is the only indicator that distinguishes the PNET group from the other 3 groups.

Pre-operative Diagnosis of Pancreatic Neuroendocrine Tumors with Endoscopic Ultrasonography and Computed Tomography in a Large Series

2016 ◽  
Vol 25 (3) ◽  
pp. 317-321 ◽  
Author(s):  
Raffaele Manta ◽  
Elisabetta Nardi ◽  
Nico Pagano ◽  
Claudio Ricci ◽  
Mariano Sica ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Neuroendocrine Tumors ◽  
Endoscopic Ultrasonography ◽  
Fine Needle Aspiration ◽  
Chromogranin A ◽  
Needle Aspiration ◽  
Large Series ◽  
Tumor Diameter ◽  
Pancreatic Neuroendocrine Tumors ◽  
Fine Needle

Background & Aims: Diagnosis of pancreatic neuroendocrine tumors (p-NETs) is frequently challenging. We describe a large series of patients with p-NETs in whom both pre-operative Computed Tomography (CT) and Endoscopic Ultrasonography (EUS) were performed. Methods: This was a retrospective analysis of prospectively collected sporadic p-NET cases. All patients underwent both standard multidetector CT study and EUS with fine-needle aspiration (FNA). The final histological diagnosis was achieved on a post-surgical specimen. Chromogranin A (CgA) levels were measured. Results: A total of 80 patients (mean age: 58 ± 14.2 years; males: 42) were enrolled. The diameter of functioning was significantly lower than that of non-functioning p-NETs (11.2 ± 8.5 mm vs 19.8 ± 12.2 mm; P = 0.0004). The CgA levels were more frequently elevated in non-functioning than functioning pNET patients (71.4% vs 46.9%; P = 0.049). Overall, the CT study detected the lesion in 51 (63.7%) cases, being negative in 26 (68.4%) patients with a tumor ≤10 mm, and in a further 3 (15%) cases with a tumor diameter ≤20 mm. CT overlooked the pancreatic lesion more frequently in patients with functioning than non-functioning p-NETs (46.5% vs 24.3%; P = 0.002). EUS allowed a more precise pre-operative tumor measurement, with an overall incorrect dimension in only 9 (11.2%) patients. Of note, the EUS-guided FNA suspected the neuroendocrine nature of tumor in all cases. Conclusions: Data of this large case series would suggest that the EUS should be included in the diagnostic work-up in all patients with a suspected p-NET, even when the CT study was negative for a primary lesion in the pancreas.– . Abbrevations: CgA: chromogranin A; EUS: Endoscopic Ultrasonography; FNA: fine-needle aspiration; p-NETs: pancreatic neuroendocrine tumors.

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