Controversies in using urine samples for prostate cancer detection: PSA and PCA3 expression analysis

PURPOSE: Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in the world. Although PSA utilization as a serum marker has improved prostate cancer detection it still presents some limitations, mainly regarding its specificity. The expression of this marker, along with the detection of PCA3 mRNA in urine samples, has been suggested as a new approach for PCa detection. The goal of this work was to evaluate the efficacy of the urinary detection of PCA3 mRNA and PSA mRNA without performing the somewhat embarrassing prostate massage. It was also intended to optimize and implement a methodological protocol for this kind of sampling. MATERIALS AND METHODS: Urine samples from 57 patients with suspected prostate disease were collected, without undergoing prostate massage. Increased serum PSA levels were confirmed by medical records review. RNA was extracted by different methods and a preamplification step was included in order to improve gene detection by Real-Time PCR. RESULTS: An increase in RNA concentration with the use of TriPure Isolation Reagent. Despite this optimization, only 15.8 percent of the cases showed expression of PSA mRNA and only 3.8 percent of prostate cancer patients presented detectable levels of PCA3 mRNA. The use of a preamplification step revealed no improvement in the results obtained. CONCLUSION: This work confirms that prostate massage is important before urine collection for gene expression analysis. Since PSA and PCA3 are prostate specific, it is necessary to promote the passage of cells from prostate to urinary tract, in order to detect these genetic markers in urine samples.

The novel prostate cancer antigen 3 (PCA3) biomarker

PCA3 is a prostate specific, nonprotein coding RNA that is significantly over expressed in prostate cancer, without any correlation to prostatic volume and/or other prostatic diseases (e.g. prostatitis). It can now easily be measured in urine with a novel transcription-mediated amplification based test. Quantification of PCA3 mRNA levels can predict the outcome of prostatic biopsies with a higher specificity rate in comparison to PSA. Several studies have demonstrated that PCA3 can be used as a prognostic marker of prostate cancer, especially in conjunction with other predictive markers. Novel PCA3-based nomograms have already been introduced into clinical practice. PCA3 test may be of valuable help in several PSA quandary situations such as negative prostatic biopsies, concomitant prostatic diseases, and active surveillance. Results from relevant clinical studies, comparative with PSA, are warranted in order to confirm the perspective of PCA3 to substitute PSA.

Determination of the association of urine prostate specific antigen levels with anthropometric variables in children aged 5-14 years

PURPOSE: Calculation of PSA is possible in human fluids even if it presents in very low concentrations with the help of hypersensitive immunodiagnostic methods. The periurethral glands represent one of the potential sources of urine prostate specific antigen (uPSA) in both sexes but the purpose of studying PSA levels in children is still unclear in the literature. In this pilot study we studied uPSA in a small cohort of normal, pre and post pubertal children, in relation to standard anthropometric variables. MATERIALS AND METHODS: The study cohort consisted of 58 children 5-14 years old (42 boys/16 girls). Height, weight, body mass index (BMI) and the respective stature-for-age, weight-for-age and BMI-for-age percentiles of the sample were determined. uPSA levels were measured using a third generation immunodiagnostic method (DPC Immulite®) that has a lower limit of detection of 3 ng/L. When levels of PSA were above the upper limit of detection, uPSA levels were assessed using the ROCHE technique. RESULTS: uPSA levels tend to be higher in male than female children (p = 0.091, linear regression analysis). uPSA was measurable only in 3/16 girls (18.75 percent). Measurable uPSA was found in 18/42 boys (42.8 percent). The range of urine PSA in boys was 0-161000 ng/L (mean 10561.9 ± 31830.48 ng/L). Statistical analysis with linear regression showed correlation with height and age in boys. CONCLUSIONS: The use of hypersensitive assays allows calculation of uPSA in childhood. The values of this variable are measurable in both sexes and related with gender. In boys, uPSA was correlated with age and height but not with other variables tested. Further studies are required to clarify this field.