Abstract
In 1999, a new prostate-specific gene was identified, prostate cancer antigen 3 (PCA3). The function of this gene remains unknown. Unlike prostate-specific antigen (PSA), PCA3 is upregulated in malignant prostatic tumours, while a low level of expression is observed in benign tumours and undetectable levels in normal tissue of several other organs. Expression of PCA3 is greatly increased in a prostate gland containing less than 10% of malignant cells. These observations have led to the development of several PCA3 assays, which measure PCA3 and PSA mRNA in prostate cells shed into the urine following prostate massage. The PCA3 (1000×[mRNA PCA3]/[mRNA PSA]) score can then be calculated. The PCA3 assay developed by Progensa is Conformité Européenne (CE)-marked and commercially available in Europe.
Auprich and collaborators performed a systematic review of the literature on PCA3 and its clinical utility. Forty-seven papers were selected after searching the PubMed database using free-text and Medical Subjects Heading (MeSH) terms and with restriction to English language.
Comparison studies demonstrated that PCA3 outperforms PSA with sensitivity and specificity reaching 82% and 76% versus 87% and 16%, respectively (uPM3 assay). The PCA3 score correlates with positive biopsy results predicting biopsy outcome, and therefore having the potential of preventing unnecessary biopsies.
When combined with PCA3, the accuracy of existing prostate cancer diagnostic tools such as ‘risk calculator’ and ‘nomogram’ was improved. Furthermore, PCA3 independently predicted small volume prostate cancer, but had limited value regarding tumour aggressiveness. The downside of PCA3 when compared with existing PSA assays is the cost per test (£300–£400 versus £5).
Recent promising results demonstrated that the association of PCA3 to other new biomarkers improves its diagnostic accuracy. Furthermore, tumours were eliminated in over 80% of mice treated with a PCA3 promoter-driven suicide gene construct, offering new perspectives for prostate cancer therapy. Further studies are required to investigate the role of PCA3 in detection and treatment of prostate cancer.