Stratification of aggressive prostate cancer from indolent disease-Prospective controlled trial utilizing expression of 11 genes in apparently benign tissue.

BACKGROUND - The aim of the study was to evaluate the diagnostic power of molecular markers in men with a clinical suspicion of prostate cancer (PCa) using apparently benign areas as targeted by magnetic resonance imaging (MRI).

METHODS - In the study, 99 consecutive men with clinical suspicion of PCa in a prospective controlled trial (IMPROD, NCT01864135) were included. In addition to 12-core systematic and MRI-targeted biopsies, cores from normal-appearing prostate areas, based on clinical examination, ultrasound, and biparametric prostate MRI, were obtained. The RNA transcript levels of ACSM1, AMACR, CACNA1D, DLX1, KLK3, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 were measured with quantitative reverse-transcription polymerase chain reaction.

RESULTS - Of the 99 men, 69 were diagnosed with PCa, 31 with primary Gleason pattern 3 and 38 with primary Gleason 4 or 5. TDRD1 messenger RNA (mRNA) levels were 1. 3 times higher (P = 0. 029) and the presence of TMPRSS2-ERG mRNAs more frequent in biopsies from men diagnosed with PCa (27/69, 39%) than in men without (5/30, 16%) (P = 0. 035). The 2 markers identified aggressive PCa defined as Gleason sum≥7 at biopsy: median TDRD1 mRNA level was 1. 4 higher (P = 0. 005) and TMPRSS2-ERG expression more frequent (P<0. 001) in high-grade cancer. A multivariate analysis of mRNA expression of 11 candidate genes combined with KLK3, serum prostate-specific antigen (PSA), percentage-free PSA, and prostate volume improved the discrimination between aggressive and nonaggressive PCa (area under the curve = 0. 77) compared with the use of the candidate genes or clinical parameters alone. However, serum PSA, percentage-free PSA, and prostate volume resulted in the best discrimination between non-organ-confined PCa (T3) from organ-confined PCa (T2) and healthy prostate (area under the curve = 0. 86).

CONCLUSIONS - Of the 11 studied genes, TDRD1 and TMPRSS2-ERG were able to statistically significantly differentiate men with PCa from men without it as single markers. However, a multivariate analysis using 15 features outperformed each individual marker in identifying aggressive PCa.

Urologic oncology. 2016 Feb 05 [Epub ahead of print]

Saeid Alinezhad, Riina-Minna Väänänen, Terhi Tallgrén, Ileana Montoya Perez, Ivan Jambor, Hannu Aronen, Esa Kähkönen, Otto Ettala, Kari Syvänen, Matthias Nees, Markku Kallajoki, Pekka Taimen, Peter J Boström, Kim Pettersson

Department of Biotechnology, University of Turku, Turku, Finland. Department of Biotechnology, University of Turku, Turku, Finland. , Department of Biotechnology, University of Turku, Turku, Finland. , Department of Information Technology, University of Turku, Turku, Finland; Department of Diagnostic Radiology, University of Turku, Finland. , Department of Diagnostic Radiology, University of Turku, Finland. , Department of Diagnostic Radiology, University of Turku, Finland; Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland. , Department of Urology, Turku University Hospital, Turku, Finland. , Department of Urology, Turku University Hospital, Turku, Finland. , Department of Urology, Turku University Hospital, Turku, Finland. , Turku Centre for Biotechnology and Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland. , Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland. , Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland. , Department of Urology, Turku University Hospital, Turku, Finland. , Department of Biotechnology, University of Turku, Turku, Finland.

PubMed