Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of chromogranin A determined by three different procedures in patients with benign diseases, neuroendocrine tumors and other malignancies

  • Research Article
  • Published:
Tumor Biology

Abstract

CgA is a tumor marker in NET's (neuroendocrine tumors) but different ranges of sensitivity and specificity according to the commercial assay kits used have been reported. Our aim was to compare three commercial available assay kits that use three different methodologies (IRMA, RIA and ELISA) to determine CgA, in a clinical setting: 52 healthy people, 98 patients with benign diseases, 94 patients with non-NET´s malignancies, 20 SCLC and in 79 patients with NET's. Results: Using a cut-off with a 100% specificity in healthy people (6 nmol/L, 60 ng/ml, and 90 ng/ml, for RIA, ELISA and IRMA, respectively), abnormal serum concentrations of CgA were found in a high proportion of patients with renal failure (76.7% ,86,7% and 93.3% with ELISA; IRMA and RIA, respectively) other benign diseases (excluding patients with creatinine concentrations > 1.5 mg/dl)(40,3%, 50% and 53,2% with ELISA, IRMA and RIA, respectively) or in patients with non-NET´s malignancies (excluding SCLC and patients with renal failure) (59,8% ELISA, 55,4%% IRMA, 37% RIA). The highest CgA sensitivity in SCLC was obtained with ELISA (100%) and in NET´s with ELISA (83.3%) and IRMA (80.3%) (RIA 65.2%). ROC curves comparing healthy people and NET´s or NET´s- benigns showed a significantly higher area under the curve (AUC) with ELISA (0.964 and 0.774), or IRMA (0.955 and 0.785), and smaller with RIA (0,806 and 0.691). Conclusions: CgA is not a specific tumormarker and abnormal concentrations may be found in non-NET´s. The higher AUC, sensitivity and specificity obtained with the ELISA and IRMA indicates that these are the best techniques to determine CgA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. McDermott EW, Guduric B, Brennan MF. Prognostic variables in patients with gastrointestinal carcinoid tumours. Br J Surg. 1994;81:1007–9.

    Article  CAS  PubMed  Google Scholar 

  2. Soga J. Carcinoids and their variant endocrinomas. An analysis of 11842 reported cases. J Exp Clin Cancer Res. 2003;22:517–30.

    CAS  PubMed  Google Scholar 

  3. Williams ED, Sandler M. The classification of carcinoid tumours. Lancet. 1963;1:238–9.

    Article  CAS  PubMed  Google Scholar 

  4. Deftos LJ. Chromogranin A: its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Endocr Rev. 1991;12:181–7.

    Article  CAS  PubMed  Google Scholar 

  5. Oberg N, Stridsberg M. Neuroendocrine tumors. In: Diamandis EP, Fritsche HA, Lilja H, Chan DW, Schwartz MK, editors. Tumor markers: physiology, pathobiology, technology and clinical applications. Washington: American Association for Clinical Chemistry Press; 2002. p. 339–50.

    Google Scholar 

  6. Campana D, Nori F, Piscitelli L, Morselli-Labate AM, Pezzilli R, Corinaldesi R, et al. Chromogranin A: is it a useful marker of neuroendocrine tumors? J Clin Oncol. 2007;25:1967–73.

    Article  CAS  PubMed  Google Scholar 

  7. Bajetta E, Ferrari L, Martinetti A, Celio L, Procopio G, Artale S, et al. Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors. Cancer. 1999;86:858–65.

    Article  CAS  PubMed  Google Scholar 

  8. Bashir S, Gibril F, Ojeaburu JV, Asgharian B, Entsuah LK, Ferraro G, et al. Prospective study of the ability of histamine, serotonin or serum chromogranin A levels to identify gastric carcinoids in patients with gastrinomas. Aliment Pharmacol Ther. 2002;16:1367–82.

    Article  CAS  PubMed  Google Scholar 

  9. Cimitan M, Buonadonna A, Cannizzaro R, Canzonieri V, Borsatti E, Ruffo R, et al. Somatostatin receptor scintigraphy versus chromogranin A assay in the management of patients with neuroendocrine tumors of different types: clinical role. Ann Oncol. 2003;14:1135–41.

    Article  CAS  PubMed  Google Scholar 

  10. Eriksson B, Arnberg H, Lindgren PG, Lorelius LE, Magnusson A, Lundqvist G, et al. Neuroendocrine pancreatic tumours: clinical presentation, biochemical and histopathological findings in 84 patients. J Intern Med. 1990;228:103–13.

    Article  CAS  PubMed  Google Scholar 

  11. Eriksson B, Oberg K, Stridsberg M. Tumor markers in neuroendocrine tumors. Digestion. 2000;62 Suppl 1:33–8.

    Article  CAS  PubMed  Google Scholar 

  12. Granberg D, Stridsberg M, Seensalu R, Eriksson B, Lundqvist G, Oberg K, et al. Plasma chromogranin A in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 1999;84:2712–7.

    Article  CAS  PubMed  Google Scholar 

  13. Nehar D, Lombard-Bohas C, Olivieri S, Claustrat B, Chayvialle JA, Penes MC, et al. Interest of chromogranin A for diagnosis and follow-up of endocrine tumours. Clin Endocrinol. 2004;60:644–52 (Oxf).

    Article  CAS  Google Scholar 

  14. Nobels FR, Kwekkeboom DJ, Coopmans W, Schoenmakers CH, Lindemans J, De Herder WW, et al. 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;82:2622–8.

    Article  CAS  PubMed  Google Scholar 

  15. Seregni E, Ferrari L, Bajetta E, Martinetti A, Bombardieri E. Clinical significance of blood chromogranin A measurement in neuroendocrine tumours. Ann Oncol. 2001;12 Suppl 2:S69–72.

    Article  PubMed  Google Scholar 

  16. Stridsberg M, Eriksson B, Oberg K, Janson ET. A comparison between three commercial kits for chromogranin A measurements. J Endocrinol. 2003;177:337–41.

    Article  CAS  PubMed  Google Scholar 

  17. Tomassetti P, Migliori M, Simoni P, Casadei R, De Iasio R, Corinaldesi R, et al. Diagnostic value of plasma chromogranin A in neuroendocrine tumours. Eur J Gastroenterol Hepatol. 2001;13:55–8.

    Article  CAS  PubMed  Google Scholar 

  18. Borch K, Stridsberg M, Burman P, Rehfeld JF. Basal chromogranin A and gastrin concentrations in circulation correlate to endocrine cell proliferation in type-A gastritis. Scand J Gastroenterol. 1997;32:198–202.

    Article  CAS  PubMed  Google Scholar 

  19. Canale MP, Bravo EL. Diagnostic specificity of serum chromogranin-A for pheochromocytoma in patients with renal dysfunction. J Clin Endocrinol Metab. 1994;78:1139–44.

    Article  CAS  PubMed  Google Scholar 

  20. Ceconi C, Ferrari R, Bachetti T, Opasich C, Volterrani M, Colombo B, et al. Chromogranin A in heart failure; a novel neurohumoral factor and a predictor for mortality. Eur Heart J. 2002;23:967–74.

    Article  CAS  PubMed  Google Scholar 

  21. Fossmark R, Jianu CS, Martinsen TC, Qvigstad G, Syversen U, Waldum HL. Serum gastrin and chromogranin A levels in patients with fundic gland polyps caused by long-term proton-pump inhibition. Scand J Gastroenterol. 2008;43:20–4.

    Article  CAS  PubMed  Google Scholar 

  22. Giusti M, Sidoti M, Augeri C, Rabitti C, Minuto F. Effect of short-term treatment with low dosages of the proton-pump inhibitor omeprazole on serum chromogranin A levels in man. Eur J Endocrinol. 2004;150:299–303.

    Article  CAS  PubMed  Google Scholar 

  23. Hirschowitz BI, Worthington J, Mohnen J, Haber M. Chromogranin A in patients with acid hypersecretion and/or hypergastrinaemia. Aliment Pharmacol Ther. 2007;26:869–78.

    Article  CAS  PubMed  Google Scholar 

  24. O'Connor DT, Pandlan MR, Carlton E, Cervenka JH, Hslao RJ. 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;35:1631–7.

    PubMed  Google Scholar 

  25. Peracchi M, Gebbia C, Basilisco G, Quatrini M, Tarantino C, Vescarelli C, et al. Plasma chromogranin A in patients with autoimmune chronic atrophic gastritis, enterochromaffin-like cell lesions and gastric carcinoids. Eur J Endocrinol. 2005;152:443–8.

    Article  CAS  PubMed  Google Scholar 

  26. Sanduleanu S, Stridsberg M, Jonkers D, Hameeteman W, Biemond I, Lundqvist G, et al. Serum gastrin and chromogranin A during medium- and long-term acid suppressive therapy: a case-control study. Aliment Pharmacol Ther. 1999;13:145–53.

    Article  CAS  PubMed  Google Scholar 

  27. Takiyyuddin MA, Parmer RJ, Kailasam MT, Cervenka JH, Kennedy B, Ziegler MG, et al. Chromogranin A in human hypertension. Influence Heredity Hypertens. 1995;26:213–20.

    CAS  Google Scholar 

  28. Waldum HL, Arnestad JS, Brenna E, Eide I, Syversen U, Sandvik AK. Marked increase in gastric acid secretory capacity after omeprazole treatment. Gut. 1996;39:649–53.

    Article  CAS  PubMed  Google Scholar 

  29. Houben P, Lundqvist G, Biedmond I, Jonkers D, Stockbrugger R. 24 hour intragastric ph, basal and meal-stimulated serum gastrin and plasma chromogranin A after short term acid inhibition. Gastroenterology. 1997;112 A 152.

  30. Portela-Gomes GM, Stridsberg M. Selective processing of chromogranin A in the different islet cells in human pancreas. J Histochem Cytochem. 2001;49:483–90.

    CAS  PubMed  Google Scholar 

  31. Stridsberg M, Hellman U, Wilander E, Lundqvist G, Hellsing K, Oberg K. Fragments of chromogranin A are present in the urine of patients with carcinoid tumours: development of a specific radioimmunoassay for chromogranin A and its fragments. J Endocrinol. 1993;139:329–37.

    Article  CAS  PubMed  Google Scholar 

  32. Zatelli MC, Torta M, Leon A, Ambrosio MR, Gion M, Tomassetti P, et al. Chromogranin A as a marker of neuroendocrine neoplasia: an Italian Multicenter Study. Endocr Relat Cancer. 2007;14:473–82.

    Article  CAS  PubMed  Google Scholar 

  33. Baudin E, Bidart JM, Bachelot A, Ducreux M, Elias D, Ruffie P, et al. Impact of chromogranin A measurement in the work-up of neuroendocrine tumors. Ann Oncol. 2001;12 Suppl 2:S79–82.

    Article  PubMed  Google Scholar 

  34. Schurmann G, Raeth U, Wiedenmann B, Buhr H, Herfarth C. Serum chromogranin A in the diagnosis and follow-up of neuroendocrine tumors of the gastroenteropancreatic tract. World J Surg. 1992;16:697–701.

    Article  CAS  PubMed  Google Scholar 

  35. Taupenot L, Harper KL, O'Connor DT. The chromogranin-secretogranin family. N Engl J Med. 2003;348:1134–49.

    Article  CAS  PubMed  Google Scholar 

  36. Bernini GP, Moretti A, Ferdeghini M, Ricci S, Letizia C, D'Erasmo E, et al. A new human chromogranin 'A' immunoradiometric assay for the diagnosis of neuroendocrine tumours. Br J Cancer. 2001;84:636–42.

    Article  CAS  PubMed  Google Scholar 

  37. Orr DF, Chen T, Johnsen AH, Chalk R, Buchanan KD, Sloan JM, et al. The spectrum of endogenous human chromogranin A-derived peptides identified using a modified proteomic strategy. Proteomics. 2002;2:1586–600.

    Article  CAS  PubMed  Google Scholar 

  38. Ferrari L, Seregni E, Lucignani G, Bajetta E, Martinetti A, Aliberti G, et al. Accuracy and clinical correlates of two different methods for chromogranin A assay in neuroendocrine tumors. Int J Biol Markers. 2004;19:295–304.

    CAS  PubMed  Google Scholar 

  39. Mountain CF. Staging classification of lung cancer. A critical evaluation. Clin Chest Med. 2002;23:103–21.

    Article  PubMed  Google Scholar 

  40. Stahel RA, Ginsberg R, Haveman K, Havemann K, Hirsch FR, Ihde DC, et al. Staging and prognostic factors in small cell lung cancer: a consensus report. Lung Cancer. 1989;5:119–26.

    Article  Google Scholar 

  41. Petterson F. Annual report on the results of treatment in gynecologic cancer, vol. 20. Stockholm: FIGO ed; 1988.

    Google Scholar 

  42. De Long ER, De Long DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristics curves: a non-parametric approach. Biometrics. 1988;44:837–45.

    Article  Google Scholar 

  43. Stephan C, Wesseling S, Schink T, Jung K. Comparison of eight computer programs for receiver-operating characteristics analysis. Cl Chem. 2003;49:433–9.

    Article  CAS  Google Scholar 

  44. Fisher JD. New York Heart Association Classification. Arch Intern Med. 1972;129:836.

    Article  CAS  PubMed  Google Scholar 

  45. Lamberts SW, Hofland LJ, Nobels FR. Neuroendocrine tumor markers. Front Neuroendocrinol. 2001;22:309–39.

    Article  CAS  PubMed  Google Scholar 

  46. Rozansky DJ, Wu H, Tang K, Parmer RJ, O'Connor DT. Glucocorticoid activation of chromogranin A gene expression. Identification and characterization of a novel glucocorticoid response element. J Clin Invest. 1994;94:2357–68.

    Article  CAS  PubMed  Google Scholar 

  47. Leon A, Torta M, Dittadi R, degli UE, Ambrosio MR, Delle FG, et al. Comparison between two methods in the determination of circulating chromogranin A in neuroendocrine tumors (NETs): results of a prospective multicenter observational study. Int J Biol Markers. 2005;20:156–68.

    CAS  PubMed  Google Scholar 

  48. Degorce F, Goumon Y, Jacquemart L, Vidaud C, Bellanger L, Pons-Anicet D, et al. A new human chromogranin A (CgA) immunoradiometric assay involving monoclonal antibodies raised against the unprocessed central domain (145-245). Br J Cancer. 1999;79:65–71.

    Article  CAS  PubMed  Google Scholar 

  49. Bajetta E, Ferrari L, Procopio G, Catena L, Ferrario E, Martinetti A, et al. Efficacy of a chemotherapy combination for the treatment of metastatic neuroendocrine tumours. Ann Oncol. 2002;13:614–21.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We declare that this research was supported by Novartis Oncology Spain. Novartis Oncology Spain has no relationship with the commercial assays used in this study and no interest in the selection of one or another method, but was interested in the standardization of the method used in the different departments of Oncology in Spain. Novartis Oncology Spain is commercially related to treatments in neuroendocrine tumors, but not in their diagnosis. This collaboration did not prejudice the impartiality of the research.

All participants collaborated in the selection of samples and in the CgA determination.

Conflict of interest

Authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Author information

Authors and Affiliations

  1. Oncobiology Unit, Laboratory of Biochemistry, Hospital Clinic of Barcelona, C/Villarroel 170, Barcelona, 08036, Spain

    Rafael Molina

  2. Servicio de Analisis Clínicos, Hospital Xeral de Vigo, Rua Pizarro 22, Vigo, 36204, Spain

    Elias Alvarez

  3. Servicio de Analisis Clínicos, Hospital cruces de Bilbao, Plaza de Cruzes s/n, Baracaldo, Bizkaia, 48903, Spain

    Angeles Aniel-Quiroga

  4. Servicio de Analisis Clínicos, Hospital Clinico de Madrid, Calle del Profesor Martin Lagos s/n, Madrid, 28040, Spain

    Maria Borque

  5. Servicio de Analisis Clínicos, Hospital de Bellvitge, Feixa Larga s/n, Hospitalet de Llobregat, Barcelona, 08097, Spain

    Belen Candás

  6. Servicio de Analisis Clínicos, Hospital Virgen del Rocio, Avenida Manuel Siurot2/n, Sevilla, 41013, Spain

    Antonio Leon

  7. Servicio de Analisis Clínicos, Hospital Virgen de las Nieves de Granada, Avda de las Fuerzas Armadas, Granada, 2, Spain

    Rafael M. Poyatos

  8. Departamento de Oncologia, Novartis, Gran via de las Corts Catalenes, Barcelona, 764, Spain

    Montserrat Gelabert

Authors
  1. Rafael Molina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elias Alvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Angeles Aniel-Quiroga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Borque
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Belen Candás
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Leon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rafael M. Poyatos
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Montserrat Gelabert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rafael Molina.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Molina, R., Alvarez, E., Aniel-Quiroga, A. et al. Evaluation of chromogranin A determined by three different procedures in patients with benign diseases, neuroendocrine tumors and other malignancies. Tumor Biol. 32, 13–22 (2011). https://doi.org/10.1007/s13277-010-0085-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-010-0085-x

Keywords

Search

Navigation