Chromogranin-A as a serum marker for neuroendocrine tumors: comparison with neuron-specific enolase and correlation with immunohistochemical findings

Int J Biol Markers. Jul-Sep 1999;14(3):160-6.


Background: Chromogranin-A (Cg-A) is a 439-amino-acid protein contained in secretory granules of neuroendocrine cells, in addition to specific hormone peptides or neuropeptides. Since Cg-A is co-released with peptide hormones its serum concentration can be used as a marker of neuroendocrine tumors.

Aim: Evaluation of the analytical performance of a new IRMA method for Cg-A assay and of the clinical value of serum Cg-A and neuron-specific enolase (NSE) in neuroendocrine tumors. In addition, we compared the diagnostic usefulness of both Cg-A and NSE serum levels and their relationship to tissue expression.

Patients and methods: Initially we evaluated the analytical performance (intra- and interassay imprecision, dilution test and detection limit) of the Cg-A RIACT method (CIS Bio-International, Gif-sur-Yvette, France). We selected 50 patients affected by various histologically confirmed neuroendocrine tumors (NETs): 111In-pentetreotide scan and helical computed tomography were employed to assess tumor extent. Cg-A and NSE were measured before surgery in serum samples of patients and 50 age-matched controls by IRMA methods. After surgery immunohistochemical stains for Cg-A and NSE were performed on surgical specimens of tumor tissue.

Results: Cg-A levels were significantly higher (p < 0.0001) in patients with NETs than in healthy controls and we found a positive correlation between serum and tissue expression (p < 0.05). Serum levels of Cg-A were also related to tumor extent (p < 0.05) but in some cases we observed significant elevation of serum Cg-A in small, intensely immunoreactive NETs. ROC curve analysis showed better accuracy for serum Cg-A compared to NSE in the diagnosis of NETs, while no significant relationship was found between serum expression and immunostaining for NSE.

Discussion: Our results confirmed the biological and clinical significance of circulating Cg-A as an expression of granular content in neuroendocrine tissues and supported the complementary usefulness of serum Cg-A in the diagnosis and evaluation of NETs together with imaging modalities.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Chromogranin A
  • Chromogranins / blood*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / diagnosis*
  • Phosphopyruvate Hydratase / blood*


  • Biomarkers, Tumor
  • CHGA protein, human
  • Chromogranin A
  • Chromogranins
  • Phosphopyruvate Hydratase