Biological variation of neuroendocrine tumor markers chromogranin A and neuron-specific enolase

Clin Biochem. 2013 Jan;46(1-2):148-51. doi: 10.1016/j.clinbiochem.2012.09.005. Epub 2012 Sep 18.


Objectives: Chromogranin A (CgA) and neuron-specific enolase (NSE) are biomarkers for neuroendocrine tumors. Although the knowledge of their biological variation (BV) is critical, only one study for CgA and no data for NSE are available. We report a definitive assessment of BV components of these biomarkers in the same cohort of subjects by an accurately experimental protocol.

Design and methods: We collected five blood specimens from each of 22 healthy volunteers (10 men and 12 women, 23-54 years) on the same day every two weeks for two months. Serum specimens were stored at -80 °C until analysis and analyzed in a single run in duplicate. Data were analyzed by ANOVA.

Results: Serum CgA concentrations were significantly higher for women than for men (P=0.01), whereas no difference was found for NSE. Intra-individual variance was not different between genders for both biomarkers. Within- and between-subject CVs were 16.3% and 33.5% for CgA and 13.6% and 11.5% for NSE, respectively. CgA showed marked individuality, suggesting that the use of population-based reference limits is inadequate for its interpretation. Conversely, the low individuality of NSE allows the use of a single reference interval. Reference change values were 46% for CgA and 39% for NSE. Desirable analytical goals for imprecision, bias, and total error were <8.2%, ±9.3%, and ±22.8% for CgA, and <6.8%, ±4.5%, and ±15.7% for NSE, respectively.

Conclusion: In this study, we defined BV components of serum CgA and NSE and derived indices that may improve the clinical use of these biomarkers.

MeSH terms

  • Adult
  • Biomarkers, Tumor / blood*
  • Chromogranin A / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / blood*
  • Phosphopyruvate Hydratase / blood*
  • Reference Values
  • Regression Analysis


  • Biomarkers, Tumor
  • Chromogranin A
  • Phosphopyruvate Hydratase