A multicenter evaluation of the PCA3 molecular urine test: Pre-analytical effects, analytical performance, and diagnostic accuracy

• Published in: Clinica chimica acta Vol. 389; no. 1-2; pp. 1 - 6
• Main Authors: Sokoll, Lori J., Ellis, William, Lange, Paul, Noteboom, Jennifer, Elliott, Debra J., Deras, Ina L., Blase, Amy, Koo, Seongjoon, Sarno, Mark, Rittenhouse, Harry, Groskopf, Jack, Vessella, Robert L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2008
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm - genetics; Antigens, Neoplasm - urine; Humans; Male; Middle Aged; Molecular urine test; PCA3; Predictive Value of Tests; Prostate cancer; Prostatic Neoplasms - diagnosis; PSA; Reproducibility of Results; RNA, Messenger - urine; Sensitivity and Specificity; PCA3; CLSI; Molecular urine test; DRE; NASBA; TMA; RLU; Prostate cancer; LOB; FMV; PSA
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2007.11.003

Measurement of prostate cancer gene 3 (PCA3) mRNA normalized to prostate-specific antigen (PSA) mRNA in urine has been proposed as a marker for prostate cancer.
We investigated pre-analytical effects, analytical performance, and diagnostic accuracy of a quantitative assay for PCA3.
Urine specimens collected without prostate manipulation demonstrated low informative rates. However, specimens collected following digital rectal examinations of 3 or 8 strokes per prostate lobe demonstrated informative rates >94%. Across all urine specimen types, median PCA3 results did not show statistically significant differences (P>0.8). Measurements of controls of known mRNA content demonstrated percent recoveries of 100±15% for both PCA3 and PSA mRNAs. PCA3 mRNA total, intra-assay, inter-assay, and inter-site CVs were ≤17.1%, ≤14.0%, ≤9.9%, and ≤3.2%, respectively. Corresponding CVs for PSA mRNA assay were ≤11.5%, ≤8.6%, ≤7.9%, and ≤8.3%. Blinded assay of urines from 72 men with known prostate biopsy outcomes yielded areas under the curve from receiver-operating characteristic analysis of 0.7 at both research sites. Deming regression of individual PCA3 results between sites yielded slope=0.94, intercept=0.48, R=0.9677 (P<0.0001).
The PCA3 assay is insensitive to pre-analytical factors, performs well analytically and correctly classifies a high percent of subjects with known prostate cancer status across research sites.