Diagnostic value of PCA3, TMPRSS2:ERG and prostatic specific antigen derivatives in the detection of prostate cancer

Abstract

Background. Prostate cancer (PCa) is one of the most common malignancy in men. A traditional marker in the laboratory diagnosis of PCa is the prostatic specific antigen (PSA). However, the low specificity of this marker leads to a large number of unnecessary biopsies. The emergence of various modifications of PSA and tumor-specific genetic markers such as PCA3 and TMPRSS2:ERG, have improved the diagnosis of PCa. Objective. Investigation of the diagnostic significance of molecular genetic markers, PCA3 and TMPRSS2:ERG, and their comparison with markers based on PSA isoforms: free/total PSA ratio (%fPSA) and prostate health index (PHI). Materials and methods. The study included 58 men with suspected PCa. All patients were defined PCA3 score and the presence of TMPRSS2:ERG fusion transcript in the urine sediment. Also, PHI and %fPSA were determined in 48 and 51 men, respectively. Results. The area under the ROC-curve regardless of the value of PSA was higher for PCA3 score (0.773, p <0.001), than for %fPSA and PHI: 0.625 (p = 0.131) and 0.735 (p = 0.006), respectively. At clinical sensitivity >95 % PCA3 score had the highest specificity, positive and negative predictive values in men, regardless of the level of PSA: 65.22, 80.95, and 93.75 %, respectively. In men with PSA level of 2–10 ng/ml the area under the ROC-curve for PCA3, %fPSA and PHI was 0.776 (p = 0.001), 0.629 (p = 0.144) and 0.729 (p = 0.009), respectively. At high sensitivity (>95 %) characteristics of the diagnostic test PCA3 in men with a PSA level of 2–10 ng/ml also also exceeded those for PHI and %fPSA. The negative predictive value for PCA3 score in this group of men was 100 %. The sensitivity of detection of the TMPRSS2:ERG fusion transcript in urine was 37.14 %, specificity 86.96 %, and the positive predictive value was 81.25 %. Conclusion. The use of the PCA3 score in combination with the detection of TMPRSS2:ERG fusion will improve the assessment of PCa risk in men with PSA levels between 2 and 10 ng/ml (the “grey zone”).