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, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2021
  • Doi Number: 10.1002/pros.24255
  • Title of Journal : PROSTATE
  • 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


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.