Introduction

While multiparametric magnetic resonance imaging (mpMRI) of the prostate has improved disease detection, up to 20% of patients with negative mpMRI harbor high grade prostate cancer (PCa). In this study, we sought to characterize and compare the molecular profiles of mpMRI visible and invisible PCa.

Methods

Patients who underwent mpMRI prior to radical prostatectomy were identified for this IRB-approved study. mpMRI for each patient was reviewed by a radiologist with expertise in prostate mpMRI and histopathology reviewed by a genitourinary pathologist. Whole-mount histopathology was co-registered with axial mpMRI images. DNA and RNA were co-isolated from all tumor foci pre-identified on formalin-fixed paraffin-embedded specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the molecular profile of each tumor focus using the Oncomine Comprehensive Panel (DNA sequencing) and a custom targeted RNAseq panel assessing PCa relevant genes. _x000D_ _x000D_ _x000D_ _x000D_

Results

A total of 26 primary tumor foci from 10 patients were analyzed. The median number of PCa foci was 3. Of the 14 (54%) invisible lesions on mpMRI, 5 (36%) were Gleason 3+4=7 (Table 1). We detected high-confidence prioritized genetic mutations in 54% (14/26) of tumor foci, 43% (6/14) of which were in mpMRI-invisible lesions. Additionally, 64% (9/14) of lesions exhibiting prioritized mutations were Gleason 7. Notable point mutations were in APC, AR, ARID1B, ATM, ATRX, BRCA2, FAT1, MAP3K1, NF1, SPEN, SPOP, TP53, and a frameshift mutation was detected in SOX2. The expression profile of mpMRI visible and invisible lesions were similar (Figure 1)._x000D_

Conclusions

We found no significant difference in the molecular profile of visible and invisible cancer foci on mpMRI. However, 36% of mpMRI invisible lesions exhibited biologically significant mutations. More work is needed to further characterize the molecular basis for mpMRI prostate cancer visibility.

Funding

None