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Prevalence and causes of abnormal PSA recovery

  • Noémie Lautenbach , Michael Müntener , Paolo Zanoni , Lanja Saleh , Karim Saba , Martin Umbehr , Srividya Velagapudi , Danielle Hof , Tullio Sulser , Peter J. Wild , Arnold von Eckardstein and Cédric Poyet EMAIL logo
Published/Copyright: August 1, 2017
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 56 Issue 2

Abstract

Background:

Prostate-specific antigen (PSA) test is of paramount importance as a diagnostic tool for the detection and monitoring of patients with prostate cancer. In the presence of interfering factors such as heterophilic antibodies or anti-PSA antibodies the PSA test can yield significantly falsified results. The prevalence of these factors is unknown.

Methods:

We determined the recovery of PSA concentrations diluting patient samples with a standard serum of known PSA concentration. Based on the frequency distribution of recoveries in a pre-study on 268 samples, samples with recoveries <80% or >120% were defined as suspect, re-tested and further characterized to identify the cause of interference.

Results:

A total of 1158 consecutive serum samples were analyzed. Four samples (0.3%) showed reproducibly disturbed recoveries of 10%, 68%, 166% and 4441%. In three samples heterophilic antibodies were identified as the probable cause, in the fourth anti-PSA-autoantibodies. The very low recovery caused by the latter interference was confirmed in serum, as well as heparin- and EDTA plasma of blood samples obtained 6 months later. Analysis by eight different immunoassays showed recoveries ranging between <10% and 80%. In a follow-up study of 212 random plasma samples we found seven samples with autoantibodies against PSA which however did not show any disturbed PSA recovery.

Conclusions:

About 0.3% of PSA determinations by the electrochemiluminescence assay (ECLIA) of Roche diagnostics are disturbed by heterophilic or anti-PSA autoantibodies. Although they are rare, these interferences can cause relevant misinterpretations of a PSA test result.

Keywords: autoantibodies; heterophilic antibodies; immunoassay; prostate-specific antigen (PSA); prostate; recovery
Corresponding author: Dr. med. Cédric Poyet, Department of Urology, University Hospital Zurich, Frauenklinikstrasse 10, 8091 Zurich, Switzerland, Phone: +41 44 255 54 03, Fax: +41 255 54 55
Noémie Lautenbach, Michael Müntener, Arnold von Eckardstein and Cédric Poyet contributed equally to this work.

Acknowledgments

This study was previously presented as a poster presentation at the EAU Annual Meeting 2016 (March 11–15, Munich, Germany) and at the AUA Annual Meeting 2016 (May 6–10, San Diego, USA) as an oral poster. Furthermore we would like to thank the following laboratories who measured recoveries by immunoassays other than the Roche Cobas ECLIA: ZLZ, Forchstrasse 361, 8008 Zürich (Advia Centaur), Laboratoire MGD, 45a route des Acacias, 1211 Genève 26 (Siemens Dimension Vista and Siemens Immulite 2000), Unilabs, Ringstrasse 12, 8600 Dübendorf (Abbott Architect), Zentrum für Labormedizin, Frohbergstrasse 3, 9001 St. Gallen (Beckman Hybritech), Laboratoire Central de Chimie Clinique, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, 1011 Lausanne (Beckman Access 2), Labor Spitäler fmi, Weissenaustr. 27, 3800 Unterseen (mini Vidas), and Laboratoire de la Clinique de La Source chemin de Pré-Fleuri 6, 1006 Lausanne (i-Chroma). We also thank Dr. Sandra Rutz from Roche diagnostics (Penzberg, Germany) for providing PSA and anti-PSA antibodies.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by an unrestricted educational grant from Abbvie, Baar, Switzerland.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplemental Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2017-0246).

Received: 2017-03-21
Accepted: 2017-07-01
Published Online: 2017-08-01
Published in Print: 2018-01-26

©2018 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2017-0246
Keywords for this article
autoantibodies; heterophilic antibodies; immunoassay; prostate-specific antigen (PSA); prostate; recovery

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Need for better PTH assays for clinical research and patient treatment
  4. Reviews
  5. Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA
  6. Hair testing of GHB: an everlasting issue in forensic toxicology
  7. Opinion Paper
  8. The use of error and uncertainty methods in the medical laboratory
  9. Genetics and Molecular Diagnostics
  10. Results of the first external quality assessment scheme (EQA) for isolation and analysis of circulating tumour DNA (ctDNA)
  11. The importance of biochemical and genetic findings in the diagnosis of atypical Norrie disease
  12. General Clinical Chemistry and Laboratory Medicine
  13. Various glycolysis inhibitor-containing tubes for glucose measurement cannot be used interchangeably due to clinically unacceptable biases between them
  14. Measurement uncertainty of γ-glutamyltransferase (GGT) in human serum by four approaches using different quality assessment data
  15. Oxidation of PTH: in vivo feature or effect of preanalytical conditions?
  16. A comparison between high resolution serum protein electrophoresis and screening immunofixation for the detection of monoclonal gammopathies in serum
  17. The key incident monitoring and management system – history and role in quality improvement
  18. Is it necessary for all samples to quantify 25OHD2 and 25OHD3 using LC-MS/MS in clinical practice?
  19. Contamination of dried blood spots – an underestimated risk in newborn screening
  20. Comparative study of the diagnostic and prognostic value of antibodies against chimeric citrullinated synthetic peptides and CCP3/CCP3.1 assays
  21. Development and validation of a multivariable prediction rule for detecting a severe acquired ADAMTS13 activity deficiency in patients with thrombotic microangiopathies
  22. Use of the sFlt-1/PlGF ratio to rule out preeclampsia requiring delivery in women with suspected disease. Is the evidence reproducible?
  23. Evaluation of a new free light chain ELISA assay: bringing coherence with electrophoretic methods
  24. Hematology and Coagulation
  25. The frequency of occurrence of fish-shaped red blood cells in different haematologic disorders
  26. Reference Values and Biological Variations
  27. Pediatric reference intervals for 29 Ortho VITROS 5600 immunoassays using the CALIPER cohort of healthy children and adolescents
  28. Cancer Diagnostics
  29. Prevalence and causes of abnormal PSA recovery
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  32. Letters to the Editor
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