Histologically benign PI‐RADS 4 and 5 lesions contain cancer‐associated epigenetic alterations. Issue 1 (21st October 2021)

• Record Type: Journal Article
• Authors: Şeref, Ceren; Acar, Ömer; Kılıç, Mert; Vural, Metin; Sağlıcan, Yeşim; Saraç, Hilal; Coşkun, Bilgen; İnce, Ümit; Esen, Tarık; Lack, Nathan A.
• Is Part Of: Prostate. Volume 82:Issue 1(2022)
• Page Start: 145
• Page End: 153
• Publication Date: 2021-10-21
• Subjects: epigenetics -- methylation biomarkers -- MRI‐guided biopsy -- multiparametric MRI -- prostate cancer; Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.24255
• Languages: English
• ISSNs: 0270-4137

Abstract

Abstract: Background: The detection rate of clinically significant prostate cancer has improved with the use of multiparametric magnetic resonance imaging (mpMRI). Yet, even with MRI‐guided biopsy 15%–35% of high‐risk lesions (Prostate Imaging‐Reporting and Data System [PI‐RADS] 4 and 5) are histologically benign. It is unclear if these false positives are due to diagnostic/sampling errors or pathophysiological alterations. To better understand this, we tested histologically benign PI‐RAD 4 and 5 lesions for common malignant epigenetic alterations. Materials and Methods: MRI‐guided in‐bore biopsy samples were collected from 45 patients with PI‐RADS 4 ( n = 31) or 5 ( n = 14) lesions. Patients had a median clinical follow‐up of 3.8 years. High‐risk mpMRI patients were grouped based on their histology into biopsy positive for tumor (BPT; n = 28) or biopsy negative for tumor (BNT; n = 17). From these biopsy samples, DNA methylation of well‐known tumor suppressor genes ( APC, GSTP1, and RARβ2 ) was quantified. Results: Similar to previous work we observed high rates of promoter methylation at GSTP1 (92.7%), RARβ2 (57.3%), and APC (37.8%) in malignant BPT samples but no methylation in benign TURP chips. Interestingly, similar to the malignant samples the BNT biopsies also had increased methylation at the promoter of GSTP1 (78.8%) and RARβ2 (34.6%). However, despite these epigenetic alterations none of these BNT patients developed prostate cancer, and those who underwent repeat mpMRI ( n = 8) demonstrated either radiological regression or stability. Conclusions: Histologically benign PI‐RADS 4 and 5 lesions harbor prostate cancer‐associated epigenetic alterations.