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. 2022 Jan;82(1):145-153.
doi: 10.1002/pros.24255. Epub 2021 Oct 21.

Histologically benign PI-RADS 4 and 5 lesions contain cancer-associated epigenetic alterations

Ceren Şeref  1 , Ömer Acar  2 , Mert Kılıç  3 , Metin Vural  4 , Yeşim Sağlıcan  5 , Hilal Saraç  1 , Bilgen Coşkun  4 , Ümit İnce  5 , Tarık Esen  2   3 , Nathan A Lack  1   6   7
Affiliations

Histologically benign PI-RADS 4 and 5 lesions contain cancer-associated epigenetic alterations

Ceren Şeref et al. Prostate. 2022 Jan.

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.

Keywords: MRI-guided biopsy; epigenetics; methylation biomarkers; multiparametric MRI; prostate cancer.

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References

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