Alpha-fetoprotein assay on dried blood spot for hepatoblastoma screening in children with Beckwith-Wiedemann syndrome and Isolated Hemihyperplasia. A. Mussa1, V. Pagliardini1, C. Molinatto1, G. Baldassarre1, A. Corrias1, F. Fagioli2, M. Cirillo Silengo1, G. B. Ferrero1 1) Department of Pediatrics, University of Torino, Torino, Italy; 2) Paediatric Onco-Haematology Unit, Regina Margherita Children's Hospital, Turin, Italy.
Beckwith-Wiedemann syndrome (BWS) and Hemihyperplasia (HH) are overgrowth disorders with embryonal tumor predisposition. As hepatoblastoma complicates 6% of cases, for its early diagnosis patients undergo a cancer screening based on the repeated dosage of the sensitive tumor marker alpha-fetoprotein (FP). However, the burden connected with the frequent blood drawns causes compliance issues and poor adherence to the surveillance protocol. Many centres opt not to perform this screening test given its unfavourable cost-effectiveness, the relatively low incidence of the tumor, and the poor adherence of the patients. We sought to analyse feasibility and reliability of FP dosage by a micromethod based on blood spot dried on filter paper (DBS), aiming at developing a reliable laboratory test more tolerable for patients. Two-hundred and fifty coupled FP determinations (plasma + DBS) collected simultaneously were compared. A hundred-two determinations were performed in 45 patients affected by BWS/HH, 147 in healthy controls, and 1 in a patients with non-syndromic hepatoblastoma. The plasma FP dosage method (AutoDELFIA hAFP, PerkinElmer) was adapted to DBS adsorbed on paper matrix for newborn screening. For the assay was used a paper disk containing 1.3 l of blood. Reaction reading was carried out by immunometric fluorimeter for delayed fluorescence of europium. There was strong correlation between plasmatic and DBS FP (r2 = 0.999, p <0.001). Cohens k coefficient for correlation was 0.96 for diagnostic cut-off of 10 U/ml (p <0.001), the threshold employed in clinical practice for tumor screening. FP determinations on serum and DBS in cases evaluated longitudinally were overlapping and highly consistent across the entire wide range of physiological fluctuations, starting from neonatal concentrations of the magnitude of 100,000 U/ml to those infantile, ranging from 0 to 10 U/ml. Longitudinal evaluations were reliable as revealed in both serum and DBS a similar physiological decreases of FP concentrations during the first years of life. DBS and plasma FP in the patient with non-syndromic hepatoblastoma were of comparable magnitude, 540 and 700 U/ml respectively, both consistent with the diagnosis. The DBS method allowed to dose FP reliably and consistently for the concentrations commonly employed in clinical practice, representing a reliable strategy for conducting cancer screening in overgrowth syndromes.
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