title: Biological variation of neuroendocrine tumor markers chromogranin A and neuron-specific enolase.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  In this study, we defined BV components of serum CgA and NSE and derived indices that may improve the clinical use of these biomarkers.
authors.affiliation: Clinical Biochemistry Laboratory, 'Luigi Sacco' University Hospital, Milano, Italy. federica.braga@unimi.it
authors.forename: Federica
authors.initials: F
authors.lastname: Braga
authors.forename: Simona
authors.initials: S
authors.lastname: Ferraro
authors.forename: Roberta
authors.initials: R
authors.lastname: Mozzi
authors.forename: Alberto
authors.initials: A
authors.lastname: Dolci
authors.forename: Mauro
authors.initials: M
authors.lastname: Panteghini
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D053379:Chromogranin A / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood*; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D012016:Reference Values; D012044:Regression Analysis
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A; D010751:Phosphopyruvate Hydratase