Use Of Chromogranin Research Articles

Plasma Progastrin-Releasing Peptide and Chromogranin A Assays for Diagnosing and Monitoring Lung Well-Differentiated Neuroendocrine Tumors: A Brief Report

IntroductionThe use of chromogranin A (CGA) as a circulating biomarker in lung carcinoids (LCs) is limited by low specificity and sensitivity. This study aimed to evaluate plasma progastrin-releasing peptide (ProGRPp) as an alternative to plasma CGA (CGAp), for the diagnosis and follow-up of LC. MethodsProGRPp and CGAp concentrations were measured in 107 patients with LC and 105 patients with benign lung disease (BLD). ResultsProGRPp distinguished patients with LC with active disease in the pretreatment (n = 43) and post-treatment (n = 43) groups from those with BLD: area under the curve for both 0.864 (p < 0.0001); sensitivity 67.4% and 58.1%, respectively; specificity 96.2%; at 64 pg/mL cutoff. CGAp failed to differentiate both LC groups from those with BLD: area under the curve 0.579 and 0.526 (for both p > 0.1); sensitivity 34.9% and 25.6%, respectively; specificity 73.3%; at 104 ng/mL cutoff. Only ProGRPp correlated with the Ki67 proliferation index (r = 0.40, p < 0.001) and was associated with mitotic count (p = 0.025), stage (p = 0.018), grade (p = 0.019), and the expression of thyroid transcription factor-1 (p = 0.005). ProGRPp had a high sensitivity (92.3%) in LC with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Abnormal postoperative ProGRPp level was associated with residual disease (p = 0.029). The changes in ProGRPp level during treatment, a decrease greater than 30% and an increase greater than 8%, were associated with image-based outcomes, partial response and disease progression, respectively (p < 0.0001). CGAp did not reflect the disease course. ConclusionsProGRPp was superior to CGAp in diagnosing LC with correlations concerning proliferation, grading, staging, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia co-occurrence, and response to treatment. ProGRPp is an optimal emerging biomarker to be further evaluated.

Use of Chromogranin A for Monitoring Patients With Pancreatic Neuroendocrine Neoplasms.

We aimed to assess the role of serum chromogranin A (CgA) in monitoring disease status and treatment response in patients with pancreatic neuroendocrine neoplasms (pNENs). We included posttherapy pNENs patients with measured serum CgA levels who underwent 68Ga-labeled tetraazacyclododecanetetraacetic acid-peptide positron emission tomography (PET) imaging between April 2017 and January 2020. Serum CgA levels were determined by enzyme-linked immunosorbent assay. Tumor response was assessed according to the PET response evaluation criteria in solid tumors. Seventy-seven patients with 101 events were included in this study. Serum CgA levels were significantly higher in patients with active disease and metastasis. The optimal cutoff values for CgA for active and metastatic pNENs diagnosis after treatment were 52.39 (77.8% sensitivity, 80.7% specificity) and 60.18 ng/mL (73.9% sensitivity, 73.1% specificity), respectively. Based on 18 patients with serial CgA measurements and PET imaging, the optimal changes in CgA levels for predicting disease remission and progression were a 28.5% decrease (71.4% sensitivity, 88.2% specificity) and a 21.0% increase (100.0% sensitivity, 75.0% specificity), respectively. We concluded that serum CgA levels are associated with disease status and treatment response and may thus provide a helpful biomarker for the monitoring and clinical management of patients with pNENs.

Chromogranin A in a Cohort of Pheochromocytomas and Paragangliomas: Usefulness at Diagnosis and as an Early Biomarker of Recurrence

ObjectiveTo evaluate the usefulness of chromogranin A (CgA) in the management of patients with pheochromocytomas (PHEOs) and paragangliomas (PGLs). MethodsWe retrospectively reviewed the charts of 132 patients with confirmed PHEOs/PGLs (PPGLs) followed at our medical center. CgA was measured in 80 patients at diagnosis. The exclusion criteria removed 19 of these patients. Five patients with relapses were also analyzed. ResultsOur cohort of 61 patients included 34 PHEOs, 14 head and neck PGLs, and 13 thoracoabdominal PGLs. CgA levels were elevated in 53 of 61 patients (86.9%) at diagnosis: 33 of 34 (97.1%) PHEOs, 9 of 14 (64.3%) head and neck paragangliomas, and 11 of 13 (84.6%) thoracoabdominal paragangliomas. For 8 of 13 (61.5%) nonfunctional PPGLs (5 head and neck paragangliomas and 3 thoracoabdominal paragangliomas), increased CgA levels showed potential as a tumor marker during follow-up. Of 10 patients with malignant PPGLs, only 1 had normal CgA levels (10.0%). Among 54 patients with PPGLs who underwent genetic testing, elevated CgA levels were positive in 73.7% of patients carrying a germline genetic variant (pathogenic and of unknown significance) versus 91.4% of patients without a known germline variant. We also report 5 PPGL cases with increased CgA levels as the first detectable marker of tumoral recurrence or progression preceding other biochemical markers or imaging. ConclusionCgA is a sensitive marker for the diagnosis of PHEO (97.1%) and thoracoabdominal paraganglioma (84.6%). CgA may be useful in the follow-up of nonfunctional PGLs and may also play a complementary role in the early detection of recurrence in secreting PPGLs.

2 - Usefulness of Chromogranin A in Diagnosis and Detection of Recurrence in Pheochromocytomas and Paragangliomas

2 - Usefulness of Chromogranin A in Diagnosis and Detection of Recurrence in Pheochromocytomas and Paragangliomas

Dynamic change of chromogranin A and synaptophysin in patients with pancreatic neuroendocrine tumor

Objective To investigate the dynamic changes of chromogranin A in patients with pancreatic neuroendocrine neoplasms after laparoscopic surgery, and to monitor the diagnosis and prognosis of patients with real-time monitoring. Methods Forty-five patients with pancreatic neuroendocrine neoplasms were enrolled in this study from March 2013 to March 2015 in First Hospita of Yulin City. All patients were underwent laparoscopic surgery. The surgical results were observed and the levels of postoperative chromogranin A were monitored. Comparisons between groups were evaluated with the χ2 test. Follow-up using telephone interview was performed to detect patients′ survival and up to January 2017. Results TNM patients with benign and malignant patients in the postoperative chromogranin A examination found that the positive expression rate were 85.0% and 53.0%, the difference between the two groups was statistically significant (P 0.05). Conclusion Endoscopic surgery for pancreatic neuroendocrine neoplasms is a minimally invasive, safe surgical approach, long-term survival rate of patients with the use of chromogranin A to monitor the level of patients after surgery can effectively assess the development and prognosis of the disease, but the synaptophysine has no significance in assessing the prognosis of the patient. Key words: Pancreatic neuroendocrine neoplasms; Chromogranin A; Laparoscopes; Prognosis

Chromogranin A and cortisol at intraoperative repeated noxious stimuli: Surgical stress in a dog model.

Objectives:Biomarkers representing sympathetic tone and the surgical stress response are measured to objectively evaluate surgical techniques and anaesthetic protocols. If a part of the intraoperative procedure is repeated on the contralateral organ, one animal may potentially serve as its own control and, if so, may minimize the problem of individual differences of the stress response to anaesthesia and surgery. This study aimed to investigate the use of chromogranin A for measurement of the intraoperative sympathetic tone. Additional aims were to investigate chromogranin A and cortisol as indicators of the intraoperative surgical stress response caused by repeated noxious stimuli in dogs subjected to ovariohysterectomy and thereby to investigate the possibility of one dog serving as its own control.Methods:Experiments were carried out on 10 dogs subjected to ovariohysterectomy. Perioperative blood samples (0–6) were collected after premedication, immediately before induction of anaesthesia (0), after induction of anaesthesia and before incision (1), before (2) and after (3) removal of the first ovary, after a 15-min pause before removal of the second ovary (4), after removal of the second ovary (5) and after closing the abdomen (6). Plasma chromogranin A and cortisol were analysed.Results:Plasma chromogranin A did not change. Plasma cortisol concentration did not change between before anaesthesia and opening of the abdomen. Plasma cortisol increased at removal of the first ovary. Cortisol did not change at removal of the second ovary but remained increased compared to initial sample.Conclusion:The results suggest chromogranin A is a poor indicator of intraoperative sympathetic tone during elective surgery in dogs. Cortisol measurement was useful for assessment of intraoperative noxious stimuli. However, at these test conditions, neither plasma chromogranin A nor plasma cortisol was useful for assessment of repeated intraoperative noxious stimuli where one dog served as its own control.

Thymic neuroendocrine tumor in a patient with multiple endocrine neoplasia type I : The limitations of surveillance

Multiple endocrine neoplasia type I (MEN1) is an autosomal dominant disorder associated with pituitary and parathyroid adenomas and neuroendocrine tumors (NETs) of the pancreas. Pancreatic NETs, most of which are non-functional, are now the primary life-threatening manifestation of MEN1. Some patients with this disorder develop NETs of the thymus, which are typically characterized by aggressive behavior and malignant potential. Although rare in the general population, 25% of all reported thymic NETs have occurred in patients with MEN1. With the aid of advancements in imaging and biomarkers, the clinician is now better equipped in detecting NETs in this high-risk group. In this report, we present a patient whose incidentally discovered thymic NET led to the diagnosis of MEN1. We provide an overview of MEN1-associated NETs with a specific focus on the use of chromogranin A (CgA) in disease surveillance.

1166P - Awareness of the Clinical Presentation and Diagnosis of Neuroendocrine Tumours in an Australian General Physician Population

ABSTRACT Background Neuroendocrine Tumours (NETs) are a rare group of malignancies where the correct diagnosis is often delayed for many years resulting in local and distant spread of the disease and mean 5 year survival rate of 30%. The diagnosis of NETs is challanging and requires the expertise of many medical specialists and diagnostic modalities. The General Physician (GP) is pivotal for early recognition, referral and management of this disease. The Unicorn Foundation, Australia's only charity directed to NET patient support, advocacy and research conducted a survey of Australian Physicians to determine knowledge of NETs. A secondary objective of the survey was to raise awareness of the disease in a broad medical population. Methods 9952 registered medical practitioners received an introductory email requesting participation in the online “NET Awareness Survey”. The questions were presented as ‘best answer’ multiple choice format with the ability to choose ‘not sure’ as an option. 26 questions covering basic NET epidemiology, clinical pathology and presentation, diagnosis and referral pattern were included. Results The survey was open from July 2011 until December 2011. A population of 9552 registered medical practitioners received the email; 38% (3630) ‘opened’ the email and 7% (655) completed the survey. Of the survey respondants, 65% (425) were General Physicians. The results of the survey indicated a lack of awareness/knowledge regarding NET epidemiology; pathology; spectrum of disease (including metastatic potential) and use of Chromogranin A as a biomarker of the disease. The majority of the respondants acknowledged the difficulties of diagnosis; the myriad presenting symptoms and association of NETs with familial syndromes. Conclusion The survey results showed that a significant proportion of General Physicians had minimal knowledge of Neuroendocrine Tumours (NETs) and their behaviour and there was a general misunderstanding of appropriate investigations to facilitate diagnosis. Improved awareness of the NETs and investigative strategies to improve diagnosis are needed amongst medical practitioners especially those in general practice. Disclosure J.C. Leyden: This research project has been supported by unrestricted educational grant from Novartis Oncology, Ipsen Pharmaceutical and Pfizer Pharmaceutical.

P-0104 Role of Chromogranin A(Cga) in Pancreatic Neuroendocrine Tumors.

IntroductionThis study was undertaken to evaluate the role of chromogranin (CGA) as a prognostic marker in the outcome of pancreatic neuroendocrine tumors (PNETs). The role of measuring chromogranin in the management of pancreatic neuroendocrine tumor is uncertain. Clinicians have used chromogranin levels to monitor progression of disease and also to assess the response to treatment. It has not been validated in any study so far. There is so far no definitive data for use of chromogranin as a prognostic biomarker in pancreatic neuroendocrine tumor (PNETs). MethodsA retrospective study of patients with PNETs seen at GHSU from 1980 to 2011 was performed. All patients (126) that have had CGA concentrations measured at least once were evaluated. Data relating to diagnosis, therapies and survival outcome were noted. Patients both unresectable and resectable disease were included. Patients who had received treatment and those who did not receive treatment with Octreotide were included. ResultsA total of 118 patients were selected, 85 patients had undergone cytoreductive surgery and rest did not have the surgery. Among the cases that had undergone cytoreductive surgery, there was a correlation between chromogranin levels and median time to death. Those patients who had a median level of less 200ng/ml had median survival of 78.625 months which was statistically improved, (p < 0.005) when compared with those with cga level of more than median level of 200ng/ml. None of the case who underwent cytoreductive surgery received octreotide as a treatment either in preop, post op or as adjuvant treatment. 33 patients did not undergo cytoreductive surgery, there was no correlation between, levels of CgA and survival. Of these only20 patients 58% (had received Octreotide and rest did not receive. Among patients who did receive Octreotide, the drop in chromogranin was statistically significant at a median of 3.6 months (p < .0.024). Patients who had a median CGA level of more than 224ng/ml had shorter survival (p < 0.005). We identified a decreased survival and an elevated CGA early post-op, within 4 months (p = 0.002). We identified increase in survival for patients with a normal CGA late post-op (between 4-12 months) with a probability in survival of 91.08 % vs 63.25.% at 4 years and median time to death of 80.265 months for normal CGA vs. 48.25 months for high CGA late post-op. ConclusionOur study shows that in patients with PNETs those who undergo cytoreductive surgery the survival was better in patients with a median CGA level of less than 200 ng/ml. Also in these patients early post-op CGA may predict clinical outcome. In patients who did not undergo cytoreductive surgery there was no correlation between CGA and survival. The role of CGA as a predictive or prospective biomarker for PNETs should be prospectively studied.

Gastroenteropancreatic (neuro)endocrine neoplasms: The histology report

Based on the year 2000 World Health Organization (WHO) classification and the European Neuroendocrine Tumor Society (ENETS) grading and staging proposals, we here define the minimal guidelines for pathology reporting of (neuro)endocrine neoplasms. The macroscopical description is recommended according to standard procedures and the microscopical description according to recognized architectural and cytological features for endocrine lesions. Minimal diagnostic immunohistochemistry entails the use of chromogranin A, synaptophysin and Ki67. Other potentially useful tests are those for CD56 N-CAM, PGP 9.5 and hormones for diagnosis, the somatostatin receptor subtype 2 for potential radiodiagnostics and therapy, and transcription factors like TTF1 and CDX2, for site of origin. Grading definition is always mandatory as well as TNM staging for surgical specimens.

Chromogranin A and the alpha-subunit of glycoprotein hormones in medullary thyroid carcinoma and phaeochromocytoma.

Using specific immunoradiometric assays, we evaluated the clinical usefulness of chromogranin A and the α-subunit of glycoprotein hormones in neuroendocrine tumours of neuroectodermic origin. The serum α-subunit of glycoprotein hormones was only slightly increased in 2 out of 44 medullary thyroid carcinoma or phaeochromocytoma patients with increased calcitonin or 24-hour urinary metanephrine levels. Serum chromogranin A was increased in 12 of 45 (27%) medullary thyroid carcinoma patients with an elevated calcitonin level and in 4 of 16 medullary thyroid carcinoma patients (25%) with an undetectable calcitonin level, in 5 of 7 phaeochromocytoma patients with increased urinary catecholamine and metabolite excretion, and in 2 of 3 patients with a non-functioning phaeochromocytoma. During follow-up, the course of chromogranin A was found to parallel that of tumour burden and/or 24-hour urinary metanephrine in 5 phaeochromocytoma patients. We conclude that chromogranin A measurement is not recommended for the diagnosis of medullary thyroid carcinoma patients. It may be useful in patients with functioning and non-functioning phaeochromocytomas as a follow-up marker. In neuroendocrine tumour patients with elevated calcitonin secretion, the serum α-subunit of glycoprotein hormone measurement may help differentiate medullary thyroid carcinoma or phaeochromocytoma patients from other endodermal-derived neuroendocrine tumour patients in whom it is frequently elevated. © 2001 Cancer Research Campaign http://www.bjcancer.com

Use of chromogranin a as specific serum marker in functioning and non-functioning digestive neuroendocrine tumors

Use of chromogranin a as specific serum marker in functioning and non-functioning digestive neuroendocrine tumors

Usefulness of chromogranin A as a marker for detection of relapses of carcinoid tumours.

It is well known that peptide-producing endocrine tumours cosecrete immunoreactive chromogranin A with their characteristic hormones. Into this study 187 patients with the diagnosis malignant carcinoids or other malignancies were entered. Using chromogranin A at a cut-off level of 30.3 U/ml it was possible to discriminate between patients in remission and patients suffering a relapse with a sensitivity of 91.7% and a specificity of 96.4%, which may be of important diagnostic value. In our study that lasted over one year we could clearly show that the measurement of chromogranin A is impressively superior to 5-hydroxyindoleacetic-acid for detecting a relapse of carcinoids.

The use of chromogranin, synaptophysin and islet amyloid polypeptide as markers for neuroendocrine tumours.

The diffuse neuroendocrine (NE) system consists of peptide hormone producing cells in different locations throughout the body (125). Usually, the cells in the anterior lobe of the pituitary, the thyroid C-cells, the parathyroid glands, the adrenal medulla. the islets of Langerhans and the hormone producing cells in the gastrointestinal tract are included in the NE system. A common feature for all these tissues and cells is their ability to secrete bioactive amines. Based on these observations, thc amine precursor uptake and decarboxylation (APUD) concept was introduced (120). IIe suggested that the NE cells were derived from cells in the neural crest which probably migrated to their final position during mbryogenesis. IIowever, there has been some debate about this concept, which has led to a re-definition of the subject. All APUD cells are peptide hormone producing cells, derived from specialised ectoderm and programmed for ultimate NE function (121).

Chromogranin A Storage and Secretion

Chromogranin A, co-stored and co-released with catecholamines from adrenal medullary and sympathetic neuronal vesicles, is elevated in the plasma of patients with pheochromocytoma. The usefulness of the hormone in the differential diagnosis of hypertension is examined. An elevated level of chromogranin A had comparable diagnostic sensitivity (83%, 24/29) to, but greater diagnostic specificity (96%, 86/90) than the level of plasma catecholamines when subjects with pheochromocytoma (n = 29) were evaluated in comparison to several reference groups, including normotensive controls (n = 49), subjects with essential hypertension (n = 28), subjects with renovascular hypertension (n = 5), and subjects with primary aldosteronism (n = 3). Subjects with signs or symptoms suggesting pheochromocytoma, but in whom the diagnosis was ultimately ruled out (n = 5) had normal plasma levels of chromogranin A. A modest rise in chromogranin A in those with essential hypertension, and correlation of chromogranin A with diastolic blood pressure in normotensive patients and patients with essential hypertension did not impair the diagnostic usefulness of chromogranin A for pheochromocytoma. Renal failure was associated with an elevated plasma chromogranin A independently of blood pressure. Plasma chromogranin A correlated with tumor mass, tumor chromogranin A content, tumor norepinephrine content, and urinary vanillylmandelic acid excretion; it did not correlate with plasma or urinary catecholamines, nor with blood pressure in patients with pheochromocytoma. Plasma chromogranin A levels did not differ in subjects with pheochromocytoma when stratified by age, sex, tumor location, or tumor pathology. Several drugs used in the diagnosis or treatment of pheochromocytoma (clonidine, metoprolol, phentolamine, and tyramine) had little effect on plasma chromogranin A concentration. Within the pheochromocytoma, chromogranin A was localized along with catecholamines to the soluble core of chromaffin granules, where it accounted for 18 +/- 5% of vesicle soluble protein. We conclude that 1) chromogranin A emerges along with catecholamines from pheochromocytoma chromaffin granules; 2) plasma chromogranin A is a sensitive and specific diagnostic tool in evaluation of actual or suspected pheochromocytoma; 3) plasma chromogranin A predicts pheochromocytoma tumor size and overall catecholamine production; and 4) drugs commonly employed in the diagnosis or treatment of pheochromocytoma have little effect on plasma chromogranin A level, preserving the usefulness of chromogranin A in evaluating pheochromocytoma. Thus, measurement of chromogranin A provides a useful adjunct to the diagnosis of pheochromocytoma.

Radioimmunoassay of chromogranin A in plasma as a measure of exocytotic sympathoadrenal activity in normal subjects and patients with pheochromocytoma.

Chromogranin A is the major soluble protein stored and secreted by exocytosis, along with catecholamines, from vesicles in the adrenal medulla and sympathetic nerves. We investigated the possible use of chromogranin A as a probe of exocytotic sympathoadrenal activity, by developing a radioimmunoassay for chromogranin A purified from pheochromocytoma vesicles. In 18 normal recumbent men chromogranin A was present in plasma at a concentration of 129 +/- 12 ng per milliliter. The concentration varied with physiologic, pharmacologic, and pathologic changes in sympathoadrenal activity. It rose with standing and fell with recumbency, though it was not perturbed by brief dynamic exercise. It rose during brief vasodilation and fell during stimulation of nonexocytotic catecholamine release by tyramine and during ganglionic blockade. The plasma concentration of chromogranin A was elevated in 11 patients with pheochromocytoma (1614 +/- 408 ng per milliliter). The mean plasma half-life was 18.4 minutes. We conclude that both resting and activated sympathoadrenal tone in normal persons, as well as catecholamine secretion by pheochromocytoma, are at least in part exocytotic in mechanism and that chromogranin A may be a useful probe of exocytotic sympathoadrenal activity.