Associations of PTEN and ERG with Magnetic Resonance Imaging Visibility and Assessment of Non-organ-confined Pathology and Biochemical Recurrence After Radical Prostatectomy

Abstract

Background: Diagnosing clinically significant prostate cancer (PCa) is challenging, but may be facilitated by biomarkers and multiparametric magnetic resonance imaging (MRI).

Objective: To determine the association between biomarkers phosphatase and tensin homolog (PTEN) and ETS-related gene (ERG) with visible and invisible PCa lesions in MRI, and to predict biochemical recurrence (BCR) and non-organ-confined (non-OC) PCa by integrating clinical, MRI, and biomarker-related data.

Design, setting, and participants: A retrospective analysis of a population-based cohort of men with PCa, who underwent preoperative MRI followed by radical prostatectomy (RP) during 2014-2015 in Helsinki University Hospital (n = 346), was conducted. A tissue microarray corresponding to the MRI-visible and MRI-invisible lesions in RP specimens was constructed and stained for PTEN and ERG.

Outcome measurements and statistical analysis: Associations of PTEN and ERG with MRI-visible and MRI-invisible lesions were examined (Pearson's χ² test), and predictions of non-OC disease together with clinical and MRI parameters were determined (area under the receiver operating characteristic curve and logistic regression analyses). BCR prediction was analyzed by Kaplan-Meier and Cox proportional hazard analyses.

Results and limitations: Patients with MRI-invisible lesions (n = 35) had less PTEN loss and ERG-positive expression compared with patients (n = 90) with MRI-visible lesions (17.2% vs 43.3% [p = 0.006]; 8.6% vs 20.0% [p = 0.125]). Patients with invisible lesions had better, but not statistically significantly improved, BCR-free survival probability in Kaplan-Meier analyses (p = 0.055). Rates of BCR (5.7% vs 21.1%; p = 0.039), extraprostatic extension (11.4% vs 44.6%; p < 0.001), seminal vesicle invasion (0% vs 21.1%; p = 0.003), and lymph node metastasis (0% vs 12.2%; p = 0.033) differed between the groups in favor of patients with MRI-invisible lesions. Biomarkers had no independent role in predicting non-OC disease or BCR. The short follow-up period was a limitation.

Conclusions: PTEN loss, BCR, and non-OC RP findings were more often encountered with MRI-visible lesions.

Patient summary: Magnetic resonance imaging (MRI) of the prostate misses some cancer lesions. MRI-invisible lesions seem to be less aggressive than MRI-visible lesions.

Keywords: Biomarkers; ERG; Multiparametric magnetic resonance imaging; PTEN; Prostate Imaging Reporting and Data System; Prostate cancer; Radical prostatectomy.