title: Pediatric population reference value distributions for cancer biomarkers and covariate-stratified reference intervals in the CALIPER cohort.
abstract: BACKGROUND
  Cancer biomarkers are commonly used in pediatrics to monitor cancer progression, recurrence, and prognosis, but pediatric reference value distributions have not been well established for these markers. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) sought to develop a pediatric database of covariate-stratified reference value distributions for 11 key circulating tumor markers, including those used in assessment of patients with childhood or adult cancers.
  
  
  METHODS
  Healthy community children from birth to 18 years of age were recruited to participate in the CALIPER project with informed parental consent. We analyzed serum samples from 400-700 children (depending on the analyte in question) on the Abbott Architect ci4100 and established reference intervals for α-fetoprotein (AFP), antithyroglobulin (anti-Tg), human epididymis protein 4 (HE4), cancer antigen 125 (CA125), CA15-3, CA19-9, progastrin-releasing peptide (proGRP), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and total and free prostate specific antigen (PSA) according to CLSI C28-A3 statistical guidelines.
  
  
  RESULTS
  We observed significant fluctuations in biomarker concentrations by age and/or sex in 10 of 11 biomarkers investigated. Age partitioning was required for CA153, CA125, CA19-9, CEA, SCC, proGRP, total and free PSA, HE4, and AFP, whereas sex partitioning was also required for CA125, CA19-9, and total and free PSA.
  
  
  CONCLUSIONS
  This CALIPER study established a database of childhood reference intervals for 11 tumor biomarkers and revealed dramatic fluctuations in tumor marker concentrations between boys and girls and throughout childhood. In addition, important differences between the adult and pediatric population were observed, further highlighting the need for pediatric-specific reference intervals.
authors.affiliation: CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada;
authors.forename: Victoria
authors.initials: V
authors.lastname: Bevilacqua
authors.affiliation: CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, and.
authors.forename: Man Khun
authors.initials: MK
authors.lastname: Chan
authors.affiliation: CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, and.
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Abbott Diagnostics, Abbott Laboratories, Abbott Park, IL.
authors.forename: David
authors.initials: D
authors.lastname: Armbruster
authors.affiliation: Abbott Diagnostics, Abbott Laboratories, Abbott Park, IL.
authors.forename: Beth
authors.initials: B
authors.lastname: Schodin
authors.affiliation: CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada;
authors.forename: Khosrow
authors.initials: K
authors.lastname: Adeli
mesh_terms: D000293:Adolescent; D000328:Adult; D057205:Automation, Laboratory / Q000295:instrumentation / Q000592:standards; D014408:Biomarkers, Tumor / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D019963:Clinical Chemistry Tests / Q000295:instrumentation / Q000592:standards; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012016:Reference Values; D012727:Sex Characteristics
chemical_list: D014408:Biomarkers, Tumor