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. 1998 Oct;78(8):1102–1107. doi: 10.1038/bjc.1998.635

Neuron-specific enolase and chromogranin A as markers of neuroendocrine tumours.

E Baudin 1, A Gigliotti 1, M Ducreux 1, J Ropers 1, E Comoy 1, J C Sabourin 1, J M Bidart 1, A F Cailleux 1, R Bonacci 1, P Ruffié 1, M Schlumberger 1
PMCID: PMC2063160  PMID: 9792158

Abstract

Circulating neuron-specific enolase (NSE) and chromogranin A (CgA) were measured in 128 patients with neuroendocrine tumours (NET) to compare their sensitivity and specificity, to investigate factors associated with elevated serum levels and to determine the usefulness of these markers in the follow-up of NET patients. NSE (Cispack NSE, Cis Bio International, Gif-sur-Yvette, France; normal <12.5 microg l(-1)), and chromogranin A (CgA-Riact, Cis Bio International, normal <100 microg l(-1)) were measured in 128 patients without renal insufficiency. There were 99 patients with gastroenteropancreatic (GEP) NET, 19 with medullary thyroid carcinoma and ten with phaeochromocytoma. Fifty-three patients with non-NET were studied as controls. Serum NSE and CgA levels were elevated in 48 (38%) and 76 (59%) of the 128 NET patients respectively. In all groups of NET patients, CgA proved to be more sensitive than NSE. NSE and CgA had a specificity of 73% and 68% respectively. Immunostaining for NSE was positive in three out of eight controls with elevated CgA levels, whereas immunostaining for CgA and synaptophysin was negative in all cases. Elevated CgA levels were significantly associated with two independent parameters, namely the presence of other secretions (P = 0.0001) and a heavy tumour burden (P = 0.001). Elevated NSE levels were exclusively associated with poor tumour differentiation (P = 0.01). Among six patients with NET followed for 11-37 months, CgA appeared to be a better marker of tumour evolution than NSE. We suggest that CgA ought to be the only general marker screened in NET patients.

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Selected References

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  1. Body J. J., Paesmans M., Sculier J. P., Dabouis G., Bureau G., Libert P., Berchier M. C., Raymakers N., Klastersky J. Monoclonal immunoradiometric assay and polyclonal radioimmunoassay compared for measuring neuron-specific enolase in patients with lung cancer. Clin Chem. 1992 May;38(5):748–751. [PubMed] [Google Scholar]
  2. Bork E., Hansen M., Urdal P., Paus E., Holst J. J., Schifter S., Fenger M., Engbaek F. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide. Eur J Cancer Clin Oncol. 1988 Jun;24(6):1033–1038. doi: 10.1016/0277-5379(88)90154-x. [DOI] [PubMed] [Google Scholar]
  3. Carney D. N., Marangos P. J., Ihde D. C., Bunn P. A., Jr, Cohen M. H., Minna J. D., Gazdar A. F. Serum neuron-specific enolase: a marker for disease extent and response to therapy of small-cell lung cancer. Lancet. 1982 Mar 13;1(8272):583–585. doi: 10.1016/s0140-6736(82)91748-2. [DOI] [PubMed] [Google Scholar]
  4. Cunningham R. T., Johnston C. F., Irvine G. B., Buchanan K. D. Serum neurone-specific enolase levels in patients with neuroendocrine and carcinoid tumours. Clin Chim Acta. 1992 Nov 30;212(3):123–131. doi: 10.1016/0009-8981(92)90179-t. [DOI] [PubMed] [Google Scholar]
  5. Deftos L. J. Chromogranin A: its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Endocr Rev. 1991 May;12(2):181–187. doi: 10.1210/edrv-12-2-181. [DOI] [PubMed] [Google Scholar]
  6. Eriksson B., Oberg K., Skogseid B. Neuroendocrine pancreatic tumors. Clinical findings in a prospective study of 84 patients. Acta Oncol. 1989;28(3):373–377. doi: 10.3109/02841868909111209. [DOI] [PubMed] [Google Scholar]
  7. Grouzmann E., Gicquel C., Plouin P. F., Schlumberger M., Comoy E., Bohuon C. Neuropeptide Y and neuron-specific enolase levels in benign and malignant pheochromocytomas. Cancer. 1990 Oct 15;66(8):1833–1835. doi: 10.1002/1097-0142(19901015)66:8<1833::aid-cncr2820660831>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  8. Hsiao R. J., Parmer R. J., Takiyyuddin M. A., O'Connor D. T. Chromogranin A storage and secretion: sensitivity and specificity for the diagnosis of pheochromocytoma. Medicine (Baltimore) 1991 Jan;70(1):33–45. [PubMed] [Google Scholar]
  9. Johnson P. W., Joel S. P., Love S., Butcher M., Pandian M. R., Squires L., Wrigley P. F., Slevin M. L. Tumour markers for prediction of survival and monitoring of remission in small cell lung cancer. Br J Cancer. 1993 Apr;67(4):760–766. doi: 10.1038/bjc.1993.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kelly R. B. Pathways of protein secretion in eukaryotes. Science. 1985 Oct 4;230(4721):25–32. doi: 10.1126/science.2994224. [DOI] [PubMed] [Google Scholar]
  11. Nobels F. R., Kwekkeboom D. J., Coopmans W., Schoenmakers C. H., Lindemans J., De Herder W. W., Krenning E. P., Bouillon R., Lamberts S. W. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones. J Clin Endocrinol Metab. 1997 Aug;82(8):2622–2628. doi: 10.1210/jcem.82.8.4145. [DOI] [PubMed] [Google Scholar]
  12. O'Connor D. T., Pandlan M. R., Carlton E., Cervenka J. H., Hslao R. J. Rapid radioimmunoassay of circulating chromogranin A: in vitro stability, exploration of the neuroendocrine character of neoplasia, and assessment of the effects of organ failure. Clin Chem. 1989 Aug;35(8):1631–1637. [PubMed] [Google Scholar]
  13. Ozturk M., Bellet D., Manil L., Hennen G., Frydman R., Wands J. Physiological studies of human chorionic gonadotropin (hCG), alpha hCG, and beta hCG as measured by specific monoclonal immunoradiometric assays. Endocrinology. 1987 Feb;120(2):549–558. doi: 10.1210/endo-120-2-549. [DOI] [PubMed] [Google Scholar]
  14. Prinz R. A., Bermes E. W., Jr, Kimmel J. R., Marangos P. J. Serum markers for pancreatic islet cell and intestinal carcinoid tumors: a comparison of neuron-specific enolase, beta-human chorionic gonadotropin and pancreatic polypeptide. Surgery. 1983 Dec;94(6):1019–1023. [PubMed] [Google Scholar]
  15. Schmechel D. E. Gamma-subunit of the glycolytic enzyme enolase: nonspecific or neuron specific? Lab Invest. 1985 Mar;52(3):239–242. [PubMed] [Google Scholar]
  16. Schürmann G., Betzler M., Buhr H. J. Chromogranin A, neuron-specific enolase and synaptophysin as neuroendocrine cell markers in the diagnosis of tumours of the gastro-entero-pancreatic system. Eur J Surg Oncol. 1990 Aug;16(4):298–303. [PubMed] [Google Scholar]
  17. Sobol R. E., Memoli V., Deftos L. J. Hormone-negative, chromogranin A-positive endocrine tumors. N Engl J Med. 1989 Feb 16;320(7):444–447. doi: 10.1056/NEJM198902163200707. [DOI] [PubMed] [Google Scholar]
  18. Tapia F. J., Polak J. M., Barbosa A. J., Bloom S. R., Marangos P. J., Dermody C., Pearse A. G. Neuron-specific enolase is produced by neuroendocrine tumours. Lancet. 1981 Apr 11;1(8224):808–811. doi: 10.1016/s0140-6736(81)92682-9. [DOI] [PubMed] [Google Scholar]
  19. Vinores S. A., Bonnin J. M., Rubinstein L. J., Marangos P. J. Immunohistochemical demonstration of neuron-specific enolase in neoplasms of the CNS and other tissues. Arch Pathol Lab Med. 1984 Jul;108(7):536–540. [PubMed] [Google Scholar]
  20. Warren W. H., Gould V. E., Faber L. P., Kittle C. F., Memoli V. A. Neuroendocrine neoplasms of the bronchopulmonary tract. A classification of the spectrum of carcinoid to small cell carcinoma and intervening variants. J Thorac Cardiovasc Surg. 1985 Jun;89(6):819–825. [PubMed] [Google Scholar]

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