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

Seref C., Acar O., Kilic M., Vural M., SAĞLICAN Y., Sarac H., ...More

PROSTATE, vol.82, no.1, pp.145-153, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 82 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1002/pros.24255
  • Journal Name: PROSTATE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, Gender Studies Database, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.145-153
  • Keywords: epigenetics, methylation biomarkers, MRI-guided biopsy, multiparametric MRI, prostate cancer, PROSTATE-CANCER, DNA METHYLATION, PROMOTER METHYLATION, CLINICAL UTILITY, BIOPSY, BIOMARKERS, MARKERS, GSTP1, HYPERMETHYLATION, PROGNOSIS
  • Acibadem Mehmet Ali Aydinlar University Affiliated: Yes


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 RAR beta 2) was quantified. Results Similar to previous work we observed high rates of promoter methylation at GSTP1 (92.7%), RAR beta 2 (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 RAR beta 2 (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.