scholarly journals Significance of chromogranin A and synaptophysin in pancreatic neuroendocrine tumors

Author(s):  
Tatsuo Tomita

The two most commonly used immunohistochemical markers for neuroendocrine cells and their tumors are chromogranin A (CgA) and synaptophysin (SPY). CgA is a marker for neuroendocrine secretory granules of four pancreatic hormones and gastrin while SPY is a marker for synaptic vesicles in neuroendocrine cells, which release classic neurotransmitters such as acetylcholine and others. CgA is involved in synthesis and secretion of peptide hormones through exocytosis while function of SPY is elusive. Thirty-five pancreatic neuroendocrine tumors (Pan-NETs) were studied, consisting of 14 insulinomas, 8 gastrinomas, 2 glucagonomas, 6 pancreatic polypeptidomas and 5 non-functioning tumors, and were immunostained for four pancreatic hormones, gastrin, CgA and SPY. Majority of Pan-NETs were less immunostained for the endocrine hormones and CgA than the normal pancreatic endocrine cells. CgA immunostaining mostly correlates with each hormone staining in non-β-cell tumors while SPY immunostaining recognizes endocrine cells diffusely in the cytoplasm. CgA immunostaining is less in insulinomas than in non-β-cell tumors, and CgA immunostaining may distinguish CgA-weaker insulinomas from CgA-stronger non-β-cell tumors. CgA immunostaining may be used as an independent marker for biological aggressiveness in non-β-cell Pan-NETs. The serum CgA levels are higher in subjects harboring non-β-cell tumors than those harboring insulinomas, and the serum CgA elevate in parallel to the increasing metastatic tumor mass. Thus, CgA positive immunostaining in Pan-NETs correlate with the elevated serum levels of CgA for diagnosing CgA-positive non-β-cell Pan-NETs and the increasing serum CgA levels indicate increasing metastatic tumor mass.

2016 ◽  
Vol 25 (3) ◽  
pp. 317-321 ◽  
Author(s):  
Raffaele Manta ◽  
Elisabetta Nardi ◽  
Nico Pagano ◽  
Claudio Ricci ◽  
Mariano Sica ◽  
...  

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.


2019 ◽  
Vol 89 (6) ◽  
pp. AB607-AB608
Author(s):  
Sandra Faias ◽  
Susana Prazeres ◽  
Mario Cunha ◽  
Ruben Roque ◽  
Luisa Pereira ◽  
...  

2017 ◽  
Vol 47 (6) ◽  
pp. 520-528 ◽  
Author(s):  
Masami Miki ◽  
Tetsuhide Ito ◽  
Masayuki Hijioka ◽  
Lingaku Lee ◽  
Kohei Yasunaga ◽  
...  

2020 ◽  
pp. 26-28
Author(s):  
N. V. Lyubimova ◽  
Yu. S. Timofeev ◽  
A. V. Lebedeva ◽  
N. E. Kushlinsky

For the first time in Russia a comparative study of chromogranin A (CgA) and chromogranin B (CgB) in neuroendocrine tumors (NETs) of the pancreas was performed. We examined 50 primary patients with pancreatic NETs and 42 healthy people. The determination of CgA and CgB was performed in blood serum using standard enzyme-linked immunoassay test-systems (Chromogranin A NEOLISA, Eurodiagnostica; Human Chromogranin B, USCN). The levels of CgA and CgB in pancreatic NETs significantly differed from the control group. There was found the association between CgA levels and the dissemination of the process, while CgB demonstrated the properties of a marker independent from the tumor dissemination. The diagnostic sensitivity of CgA was 76 %, CgB – 68 %. Complex determination of CgA and CgB enhanced the diagnostic sensitivity to 84 %. Our data indicate the potential usefulness of complex CgA and CgB in the diagnosis of pancreatic NETs.


1987 ◽  
Vol 35 (7) ◽  
pp. 795-801 ◽  
Author(s):  
S A Hearn

An antibody (LK2H10) to chromogranin A has been recommended for use in ultrastructural identification of neuroendocrine secretory granules. Previous studies have demonstrated immunoreactive chromogranin A in specimens prepared for electron microscopy by glutaraldehyde fixation only. In this study, the effect of specimen post-fixation by osmium tetroxide on post-embedding localization of chromogranin A was evaluated. Human tissues from benign endocrine glands, neuroendocrine tumors, and non-neuroendocrine tumors were post-fixed in osmium, embedded in epoxy resin, and the sample thin sections immunolabeled using a protein A-gold technique. Chromogranin A-positive neurosecretory granules were detected in pancreatic islets, adrenal medulla, stomach, ileum, anterior pituitary, and parathyroid. Mid-gut carcinoids, bronchial carcinoids, pheochromocytomas, paragangliomas, carotid body tumors, and thyroid medullary carcinomas contained immunoreactive granules. Cytoplasmic granules in non-neuroendocrine tumors did not react for chromogranin A. Tissues post-fixed in osmium tetroxide had optimally preserved ultrastructural features, and use of this fixative is compatible with postembedding localization of chromogranin A in neurosecretory granules.


2003 ◽  
pp. 39-43 ◽  
Author(s):  
M Peracchi ◽  
D Conte ◽  
C Gebbia ◽  
C Penati ◽  
S Pizzinelli ◽  
...  

OBJECTIVE: As circulating chromogranin A (CgA) has been claimed to be the best general neuroendocrine marker so far available, we evaluated the usefulness of CgA determination in the clinical assessment of patients with sporadic gastro-entero-pancreatic neuroendocrine tumors (GEP NETs) or multiple endocrine neoplasia type 1 (MEN 1). DESIGN AND METHODS: Plasma CgA levels were measured using a commercial enzyme-linked immunosorbent assay in 61 patients with sporadic GEP NET and in 25 with MEN 1 including 16 with GEP NET. Controls were 50 healthy volunteers, 46 patients with pituitary adenoma and 35 patients with primary hyperparathyroidism. RESULTS: The cutoff value for CgA established in our healthy subjects (as mean+2 s.d.) was 20 U/l. CgA levels were above the normal range in 71/77 patients with sporadic or MEN 1-related GEP NETs (92%), in four out of nine MEN 1 patients without GEP NETs (44%), and only in 22/81 control patients with pituitary or parathyroid disease (27%). Furthermore, CgA levels of over 100 U/l occurred in 36/77 patients with GEP NETs (47%) and only in one patient with a non-functioning pituitary adenoma. In the patients with GEP NETs, both tumor burden and secretory activity affected CgA levels, and successful surgical resection was associated with markedly decreased CgA values. CONCLUSIONS: Plasma CgA was confirmed to be a reliable marker for GEP NETs. Moreover, in MEN 1 patients the finding of very high CgA levels strongly suggests the presence of a GEP NET, as both primary hyperparathyroidism and pituitary adenomas rarely cause marked CgA increases.


Surgery ◽  
2019 ◽  
Vol 165 (4) ◽  
pp. 760-766 ◽  
Author(s):  
Mustafa Raoof ◽  
Zeljka Jutric ◽  
Laleh G. Melstrom ◽  
Byrne Lee ◽  
Daneng Li ◽  
...  

2010 ◽  
Vol 29 (4) ◽  
pp. 254-264 ◽  
Author(s):  
Anna Tzontcheva

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.


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