Within- and between-subject biological variation data for tumor markers based on the European Biological Variation Study

Abdurrahman Coşkun (Lead / Corresponding author), Aasne K. Aarsand, Sverre Sandberg, Elena Guerra, Massimo Locatelli, Jorge Díaz-Garzón, Pilar Fernandez-Calle, Ferruccio Ceriotti, Niels Jonker, William A. Bartlett, Anna Carobene, European Federation of Clinical Chemistry,

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)
54 Downloads (Pure)


Objectives: Reliable biological variation (BV) data are required for the clinical use of tumor markers in the diagnosis and monitoring of treatment effects in cancer. The European Biological Variation Study (EuBIVAS) was established by the EFLM Biological Variation Working Group to deliver BV data for clinically important measurands. In this study, EuBIVAS-based BV estimates are provided for cancer antigen (CA) 125, CA 15-3, CA 19-9, carcinoembryonic antigen, cytokeratin-19 fragment, alpha-fetoprotein and human epididymis protein 4.

Methods: Subjects from five European countries were enrolled in the study, and weekly samples were collected from 91 healthy individuals (53 females and 38 males; 21-69 years old) for 10 consecutive weeks. All samples were analyzed in duplicate within a single run. After excluding outliers and homogeneity analysis, the BVs of tumor markers were determined by CV-ANOVA on trend-corrected data, when relevant (Røraas method).

Results: Marked individuality was found for all tumor markers. CYFRA 21-1 was the measurand with the highest index of individuality (II) at 0.67, whereas CA 19-9 had the lowest II at 0.07. The CV I s of HE4, CYFRA 21-1, CA 19-9, CA 125 and CA 15-3 of pre- and postmenopausal females were significantly different from each other.

Conclusions: This study provides updated BV estimates for several tumor markers, and the findings indicate that marked individuality is characteristic. The use of reference change values should be considered when monitoring treatment of patients by means of tumor markers.

Original languageEnglish
Pages (from-to)543-552
Number of pages10
JournalClinical Chemistry and Laboratory Medicine (CCLM)
Issue number4
Early online date10 May 2021
Publication statusPublished - 1 Mar 2022


  • Adult
  • Aged
  • Antigens, Neoplasm
  • Biological Variation, Population
  • Biomarkers, Tumor
  • Female
  • Humans
  • Keratin-19
  • Male
  • Middle Aged
  • Young Adult
  • tumor markers
  • biological variation
  • cancer

ASJC Scopus subject areas

  • Biochemistry, medical
  • Clinical Biochemistry


Dive into the research topics of 'Within- and between-subject biological variation data for tumor markers based on the European Biological Variation Study'. Together they form a unique fingerprint.

Cite this