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

: Alinezhad S, Vaananen RM, Tallgren T, Perez IM, Jambor I, Aronen H, Kahkonen E, Ettala O, Syvanen K, Nees M, Kallajoki M, Taimen P, Bostrom PJ, Pettersson K

Publisher: ELSEVIER SCIENCE INC

: 2016

: Urologic Oncology: Seminars and Original Investigations

: UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS

: UROL ONCOL-SEMIN ORI

: JUN 2016

: 34

: 6

: 255.e15

: 255.e22

: 8

: 1078-1439

: 1873-2496

DOI: https://doi.org/10.1016/j.urolonc.2015.12.014

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: hi the study, 99 consecutive men with clinical suspicion of PCa in a prospective controlled trial (IMPROD, NCT01864135) were included. hi 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 polymerise 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. (c) 2016 Elsevier Inc. All rights reserved.