Clinical significance of elevated serum chromogranin A levels

Background: Chromogranin A (CgA) has been shown to be a useful marker in the diagnosis of neuroendocrine (NE) tumours. The clinical significance of CgA has been studied mostly in patients with known NE tumours. The diagnosis was evaluated in 153 consecutive patients in whom CgA was measured in a given time interval. Methods: CgA in serum was measured by radioimmunoassay. Immunohistochemistry with an antibody against CgA was performed in tumours from patients with adenocarcinoma and elevated CgA levels using a conventional method and the more sensitive tyramide signal amplification (TSA) technique. Results: Elevated serum CgA levels were found in 44 patients; 19 had NE tumours and 6 had tumours classified as adenocarcinomas. With the TSA technique, a high proportion of CgA‐positive cells were disclosed in five of the adenocarcinoma patients. Patients with atrophic gastritis (no. 2) and patients treated with inhibitors of gastric acid secretion (no. 6) also had elevated levels of CgA. A modest increase in CgA levels was observed in 2 patients with renal impairment, and in 9 patients without any obvious cause. Conclusion: The current study confirms that serum CgA is a sensitive marker for the detection of NE neoplasia. Elevated levels found in patients with adenocarcinoma may indicate NE differentiation in the tumour. CgA is a useful tool in the monitoring of enterochromaffin‐like (ECL) hyperplasia secondary to treatment with acid secretion inhibitors or atrophic gastritis.

[1]  G. Qvigstad,et al.  Detection of Chromogranin A in Human Gastric Adenocarcinomas using a Sensitive Immunohistochemical Technique , 2000, The Histochemical Journal.

[2]  K. Tsao,et al.  Elevated serum chromogranin A is detectable in patients with carcinomas at advanced disease stages. , 2000, Annals of clinical and laboratory science.

[3]  E. Seregni,et al.  Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors , 1999, Cancer.

[4]  C. Stratakis,et al.  Adrenocortical Tumors: Recent Advances in Basic Concepts and Clinical Management , 1999, Annals of Internal Medicine.

[5]  D. Venzon,et al.  Prospective study of the value of serum chromogranin A or serum gastrin levels in the assessment of the presence, extent, or growth of gastrinomas , 1999, Cancer.

[6]  S. Falkmer,et al.  Clinical and histopathological tumour progression in ECL cell carcinoids (“ECLomas”) , 1999, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[7]  E. Baudin,et al.  Neuron-specific enolase and chromogranin A as markers of neuroendocrine tumours. , 1998, British Journal of Cancer.

[8]  E. Krenning,et al.  Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones. , 1997, The Journal of clinical endocrinology and metabolism.

[9]  L. Holmberg,et al.  Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center. , 1997, Annals of oncology : official journal of the European Society for Medical Oncology.

[10]  J. Rehfeld,et al.  Basal chromogranin A and gastrin concentrations in circulation correlate to endocrine cell proliferation in type-A gastritis. , 1997, Scandinavian journal of gastroenterology.

[11]  A. Sandvik,et al.  Marked increase in gastric acid secretory capacity after omeprazole treatment. , 1996, Gut.

[12]  N. Leonard,et al.  Neuroproliferation in the mucosa is a feature of coeliac disease and Crohn's disease. , 1995, Gut.

[13]  D. O'Connor,et al.  Chromogranin A and pancreastatin‐like immunoreactivity in human carcinoid disease , 1993 .

[14]  D. O'Connor,et al.  Rapid, high-yield isolation of human chromogranin A from chromaffin granules of pheochromocytomas , 1992, Neuropeptides.

[15]  P. Scardino,et al.  Elevated plasma chromogranin-A concentrations in prostatic carcinoma. , 1991, The Journal of urology.

[16]  D. O'Connor,et al.  Suppression of chromogranin-A release from neuroendocrine sources in man: pharmacological studies. , 1991, The Journal of clinical endocrinology and metabolism.

[17]  D. O'Connor,et al.  Chromogranin A Storage and Secretion: Sensitivity and Specificity for the Diagnosis of Pheochromocytoma , 1991, Medicine.

[18]  D. O'Connor,et al.  Chromogranin A in children with neuroblastoma. Serum concentration parallels disease stage and predicts survival. , 1990, The Journal of clinical investigation.

[19]  D. O'Connor,et al.  Chromogranin A. Storage and release in hypertension. , 1990, Hypertension.

[20]  D. O'Connor,et al.  Chromogranin A in uremia: progressive retention of immunoreactive fragments. , 1990, Kidney international.

[21]  D. O'Connor,et al.  Elevated serum chromogranin A concentrations in small-cell lung carcinoma. , 1986, Annals of internal medicine.

[22]  D. O'Connor.  Plasma Chromogranin A Initial Studies in Human Hypertension , 1985, Hypertension.

[23]  C. Silfverswärd,et al.  Paragangliomas: Neuroendocrine features and cytometric DNA distribution patterns , 2005, Virchows Archiv A.

[24]  M. Stridsberg,et al.  Neuroendocrine differentiation in carcinomas of the prostate: Do neuroendocrine serum markers reflect immunohistochemical findings? , 1997, The Prostate.

[25]  M. Stridsberg,et al.  Chromogranin A and chromogranin B are sensitive circulating markers for phaeochromocytoma. , 1997, European journal of endocrinology.

[26]  J. Polak.  Diagnostic histopathology of neuroendocrine tumours , 1993 .

[27]  N. Havu.  Enterochromaffin-like cell carcinoids of gastric mucosa in rats after life-long inhibition of gastric secretion. , 1986, Digestion.