Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer

Stephen D. Mikolajczyk*, William J. Catalona, Cindy L. Evans, Harry J. Linton, Lisa S. Millar, Kathy M. Marker, Diksha Katir, Anna Amirkhan, Harry G. Rittenhouse

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

Abstract

Introduction: Pro or precursor forms of prostate-specific antigen (PSA) have emerged as potentially important diagnostic serum markers for prostate cancer detection. Immunoassays were developed to measure specific proPSA forms containing propeptides of 2, 4, and 7 amino acids [(-2)proPSA, (-4)proPSA, and (-7)proPSA, respectively]. Methods: Research-use dual monoclonal antibody immunoassays using europium-labeled detection monoclonal antibodies were developed for each form of proPSA. Sera from patients with prostate cancer or benign prostate disease containing 4-10 μg/L PSA were assayed and analyzed by area under the ROC curve (AUC) for specificity and sensitivity. Results: The proPSA forms had quantification limits of 0.015-0.025 μg/L in serum, with cross-reactivities <1% with PSA. The sum of the proPSA forms divided by free PSA (percentage proPSA) had a higher AUC than did percentage of (-2)proPSA, free PSA, and complexed PSA with AUC (95% confidence intervals) of 0.69 (0.64-0.74), 0.64 (0.58-0.68), 0.63 (0.58-0-68), and 0.57 (0.51-0.62), respectively. The proPSA comprised a median of 33% of the free PSA in cancer and 25% in noncancer sera (P <0.0001). One-third (33%) of cancer samples had >40% proPSA, whereas only 8% of noncancer samples did (P <0.0001). In men with cancer and >25% free PSA, the (-2)proPSA had an AUC of 0.77 (0.66-0.86), with 90% sensitivity and 36% specificity at 0.04 μg/L. Conclusions: The percentage of proPSA gave better cancer detection in the 4-10 μg/L range than did percentage of free PSA and complexed PSA. (-2)proPSA significantly discriminated cancer in men whose serum had >25% free PSA, for whom there is currently no good marker for cancer detection.

Original languageEnglish (US)
Pages (from-to)1017-1025
Number of pages9
JournalClinical chemistry
Volume50
Issue number6
DOIs
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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