Abstract
Serum chromogranin A (CgA) is a useful marker for neuroendocrine tumors and is detectable in carcinomas at advanced stages. Elevated serum CgA is also an indicator of poor prognosis in prostate cancer and is useful for predicting the failure of hormonal therapy for prostate cancer patients. We found that CgA molecules with three different sizes could be detected in normal human serum. However, only the largest CgA molecule appears in patients with liver disease. Serum taken from cancer patients is composed predominantly of the middle‐sized molecule, whereas the smallest CgA molecule was elevated in serum drawn from renal patients. Moreover, only the smallest CgA molecule was found in urine. We believe that the largest CgA molecule is metabolized by the liver, whereas the smallest CgA molecule is removed from the blood circulation via the kidney. Because the medium‐sized CgA is the dominant molecule in both the cell medium of the tumor cell line SK‐N‐AS and sera from patients with malignant diseases, CgA from the cell medium was selected as the calibrator for the CgA ELISA assay. Our findings also suggest that it would not be possible to measure the urinary CgA to reflect the serum CgA concentration in order to detect pheochromocytoma among patients with hypertension. J. Clin. Lab. Anal. 15:193–198, 2001. © 2001 Wiley‐Liss, Inc.
Keywords: chromogranin A, size heterogeneity, chromatography, neuroendocrine, calibrator, ELISA
REFERENCES
- 1. Deftos LJ. 1991. Chromogranin A. Its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Endocr Rev 12:181–186. [DOI] [PubMed] [Google Scholar]
- 2. O’Connor DT, Deftos LJ. 1986. Secretion of chromogranin A by peptide‐producing endocrine neoplasm. N Engl J Med 314:1145–1151. [DOI] [PubMed] [Google Scholar]
- 3. Nobels FR, Kwekkeboom DJ, Bouillon R, Lamberts SW. 1998. Chromogranin A: its clinical value as marker of neuroendocrine tumours. Eur J Clin Invest 28:431–440. [DOI] [PubMed] [Google Scholar]
- 4. Hsiao RJ, Seeger RC, Yu AL, O’Connor DT. 1990. Chromogranin A in children with neuroblastoma. Serum concentration parallels disease stage and predicts survival. J Clin Invest 85:1555–1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Baudin E, Gigliotti A, Ducreux M, Bonacci R, Ruffie P, Schlumberger M, Ropers J, Comoy E, Sabourin JC, Bidart JM, Cailleux AF. 1988. Neuron‐specific enolase and chromogranin A as markers of neuroendocrine tumours. Br J Cancer 78:1102–1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Deftos LJ. 1991. Chromogranin A‐Its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Endocr Rev 12:181–287. [DOI] [PubMed] [Google Scholar]
- 7. Eisenhofer G, Lenders JW, Linehan WM, Walther MM, Goldstein DS, Keiser HR. 1999. Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel‐Lindau disease and multiple endocrine neoplasia type 2. N Engl J Med 340:1872–1879. [DOI] [PubMed] [Google Scholar]
- 8. Di Sant’Agnese P. 1995. Neuroendocrine differentiation in prostatic carcinoma. Cancer 75:1850–1859. [Google Scholar]
- 9. Wu JL, Erickson AJ, Tsao K‐C, Wu T‐L, Sun C‐F. 2000. Elevated serum chromogranin A is detectable in patients with carcinomas at advanced disease stages. Ann Clin Lab Sci 30:175–178. [PubMed] [Google Scholar]
- 10. Wu JT, Astill ME, Liu GH, Stephenson RA. 1998. Serum chromogranin A: early detection of hormonal resistance in prostate cancer patients. J Clin Lab Anal 12:20–25. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Wu TL, Chang PY, Tsao K‐C, Sun CF, Wu JT. 1999. Development of a microplate assay for serum chromogranin A (CgA): establishment of normal reference values and the detection of elevated CgA in carcinomas. J Clin Lab Anal 13:312–319. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Corti A, Gasparri A, Chen FX, Pelagi M, Brandaza A, Sidoli A, Siccardi AG. 1996. Characterisation of circulating chromogranin A in human cancer patients. Br J Cancer 73:924–932. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Crawford GA, Gyory AZ, Dallery DM, Kelly D. 1990. HPLC of urinary catecholamines in the presence of labetalol, captopril, and α‐methyldopa. Clin Chem 36:1849–1853. [PubMed] [Google Scholar]
- 14. Eder U, Fischer‐Colbrie R, Kogner P, Leitner B, Bjellerup P, Winkler H. 1998. Levels and molecular forms of chromogranins in human childhood neuroblastomas and ganglioneuromas. Neurosci Lett 253:17–20. [DOI] [PubMed] [Google Scholar]