Prognostic and predictive molecular biological markers in prostate cancer – significance of expression of genes PCA3 and TMPRSS2

R. SOUMAROVA, A. BODAY, V. KRHUTOVA, A. JANOTOVA, M. DVORAKOVA, E. JALUVKOVA, M. STURSA, H. PERKOVA

Abstract:

Prostate specific antigen and digital rectal examination have low specificity for detecting prostate cancer and they poorly predict the presence of aggressive disease. We present recent findings on PCA3 and TMPRSS:ERG fusion and assessed the relationship between PSA, urine PCA3 and TMPRSS2:ERG and corelation with pathological findings. We tested the PCA3 score in two groups. The first comprised 96 men treated in urology out-patient units with suspicion of prostate cancer, who had elevated PSA and/or positive DRE. The second group comprised 28 patients, who were treated by radiation for localised prostate cancer, and whose PCA3 was regularly monitored. A further cohort comprised patients with already-diagnosed tumors, who had undergone radical prostatectomy. With these, using histopathological samples, we examined samples of the TMPRSS2:ERG fusion gene and compared the results with Gleason score values and level of PSA. We also examined the TMPRSS2:ERG gene in patients who had positive biopsy. Part of the genetical analysis was also an examination of the MSMB gene.The sensitivity of PCA3 testing was 66.7% and the specificity 78.5%. TMPRSS2:ERG gene was correllated with the Gleason score. Neither the TMPRSS2:ERG (p=0.13) nor the MSMB (p=0.556) genotype had an influence on the value of the Gleason score. However a difference was found between the homozygote and wild type (WT) in the TMPRSS2 gene.FISH analysis of TMPRSS/ERG gene fusion was evaluated as positive in 8 (36.8%) of the biopsically verified tumors and in 20 (37.3%) of the evaluated patients after RAPE of parafin slicing.We did not confirm a corellation between fusion and Gleason score (p=0.29).PCA3, with its higher sensitivity in comparison with PSA, is more useful for eventual screening examination. Identification of further molecular markers such as TMPRSS2, may be very promising ways to determine further prognosis of patients with prostate cancer.