The role of PCA3 in the diagnosis of prostate cancer.

Abstract

Serum PSA has shown to be the most valuable tool in the detection, staging and monitoring of prostate cancer (PCa). However, the substantial overlap in serum PSA values between men with non-malignant prostatic diseases and PCa is the limitation of PSA as a prostate tumor marker. In patients with serum PSA values between 3-10 ng/ml, the negative biopsy rate is 60-75%. In this thesis, the focus is on improving the specificity in PCa diagnosis by using PCa-specific genes in adjunct to serum PSA testing. Prostate cancer gene 3 (PCA3) was identified as the prime candidate biomarker for the detection of PCa. The strong association between PCA3 over-expression and malignant transformation of prostate epithelium has prompted its potential use as a biomarker for the diagnosis of PCa. Since PCA3 is a non-coding RNA, an RNA-based molecular assay for PCA3 was developed. The studies in this thesis demonstrated and validated the potential of an RUO quantitative PCA3-based urine test to detect PCa cells in urinary sediments after digital rectal examination (DRE) and showed that PCA3 could aid in the prediction of biopsy outcome. PCa is a heterogeneous disease and the combination of tests for PCA3 and TMPRSS2-ERG gene-fusions were shown to improve the sensitivity without compromising specificity. In 2006, the RUO-PCA3 test has been translated to an IVD validated technology platform (Gen-Probe Inc.) and the CE-marked version of this test is the first, fully translated RNA-based molecular diagnostic urine test for PCa that is now available to urologists. This test can contribute to the decision making in the diagnosis of PCa. The value of the PCA3 test to predict the biological behaviour of prostate tumors is not fully matured, although some studies show promising results. Non-invasive biomarker-based assays for the diagnosis of PCa have now become reality.