Prostate CancerPerformance of Prostate Cancer Antigen 3 (PCA3) and Prostate-Specific Antigen in Prescreened Men: Reproducibility and Detection Characteristics for Prostate Cancer Patients with High PCA3 Scores (≥100)
Introduction
The prostate cancer gene 3 (DD3), now known as prostate cancer antigen 3 (PCA3), was identified in 1999. A DD3-based quantitative reverse transcriptase-polymerase chain reaction assay was developed to determine PCA3 in prostate cells shed into the urine after rectal examination [1], [2], [3], [4].
The difference in expression of PCA3 between normal prostate cells and prostate cancer (PCa) cells is large, qualifying the test as more specific for PCa than serum prostate-specific antigen (PSA). Such a test is obviously needed to improve on PSA, which is prostate specific but not cancer specific [5].
The high level of specificity of PCA3 in prostate tissues created an expectation for PCA3 in cells shed into urine, and thus the positive predictive value (PPV) after biopsy should be high. A rebiopsy should be considered in men who have a high PCA3 score and a negative biopsy result. In our previous publication [6] on 721 men who were all biopsied, only 28 of 90 men with a PCA3 score ≥100 had a positive lateralized sextant biopsy (PPV: 31.1%), although the specificity was 90%. This warranted further research, which is described in this paper.
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Material and methods
We further assessed men with high PCA3 scores and negative biopsy results in the PCA3 study within the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, performed earlier [6]. Repeat PCA3 testing and biopsy were performed in men with a PCA3 score ≥100 as well as in a randomly assigned control population of men with PCA3 scores <100. The study had three objectives: (1) to compare PCA3 scores obtained from retesting of archived urine specimens with the value
Part 1: Reevaluation of prostate cancer antigen 3 on original urine samples
The stored urine samples of 83 men (PCA3 score ≥100) and 117 men (PCA3 score <100) were retested in San Diego in January 2009 (Fig. 1). The PCA3 scores <100 were confirmed in 96.5% and the original PCA3 scores ≥100 in 50.6% of cases. This discrepancy was attributed to gel formation in the urine specimens in San Diego. Investigation performed by Gen-Probe indicated that overnight thawing caused the gelling, resulting in nonhomogeneous specimens, and the automated pipetter did not obtain an
Discussion
Part 1 of our evaluation described the retesting of archived frozen urine specimens. During this analysis, it became obvious that specimen thawing/handling can affect assay results, especially when using the Tecan automated pipette (Tecan Group, Männedorf, Switzerland). This problem is addressed in the manufacturer’s labeling. Discrepancy between the original and retest PCA3 scores due to assay variability seems unlikely. High concordance was shown when separate laboratories tested the same
Conclusions
Our data reveal an increase of the PPV to a level similar to those reported from other studies of men with PCA3 scores ≥100, which average 59%. PCA3 specificity is consistent with previous reports. These findings do not offer a direct explanation why PCA3 scores can be excessively high in spite of the absence of biopsy-detectable PCa. Longer follow-up of these men might provide more information. Changes over time of PSA and PCA3 are different with considerably more decreasing PCA3 values.
References (19)
- et al.
uPM3, a new molecular urine test for the detection of prostate cancer
Urology
(2004) - et al.
PCA3: a molecular urine assay for predicting prostate biopsy outcome
J Urol
(2008) - et al.
Performance of the prostate cancer antigen 3 (PCA3) gene and prostate-specific antigen in prescreened men: exploring the value of PCA3 for a first-line diagnostic test
Eur Urol
(2010) - et al.
Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram
J Urol
(2007) - et al.
A multicenter evaluation of the PCA3 molecular urine test: pre-analytical effects, analytical performance and diagnostic accuracy
Clin Chim Acta
(2008) - et al.
PCA3 urine mRNA testing for prostate carcinoma: patterns of use by community urologists and assay performance in a reference laboratory setting
Urology
(2009) - et al.
PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy
Urology
(2007) - et al.
Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy
Eur Urol
(2008) - et al.
Identification of PCA3 (DD3) in prostatic carcinoma by in situ hybridization
Mod Pathol
(2007)
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Urinary PCA3 to predict prostate cancer in a cohort of 1015 patients
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