{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:24:54Z","timestamp":1772756694135,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The detection rate of clinically significant prostate cancer has improved with the use of multiparametric magnetic resonance imaging (mpMRI). Yet, even with MRI\u2010guided biopsy 15%\u201335% of high\u2010risk lesions (Prostate Imaging\u2010Reporting and Data System [PI\u2010RADS] 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\u2010RAD 4 and 5 lesions for common malignant epigenetic alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>MRI\u2010guided in\u2010bore biopsy samples were collected from 45 patients with PI\u2010RADS 4 (<jats:italic>n<\/jats:italic>\u2009=\u200931) or 5 (<jats:italic>n<\/jats:italic>\u2009=\u200914) lesions. Patients had a median clinical follow\u2010up of 3.8 years. High\u2010risk mpMRI patients were grouped based on their histology into biopsy positive for tumor (BPT; <jats:italic>n<\/jats:italic>\u2009=\u200928) or biopsy negative for tumor (BNT; <jats:italic>n<\/jats:italic>\u2009=\u200917). From these biopsy samples, DNA methylation of well\u2010known tumor suppressor genes (<jats:italic>APC<\/jats:italic>, <jats:italic>GSTP1<\/jats:italic>, and <jats:italic>RAR\u03b22<\/jats:italic>) was quantified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Similar to previous work we observed high rates of promoter methylation at <jats:italic>GSTP1<\/jats:italic> (92.7%), <jats:italic>RAR\u03b22<\/jats:italic> (57.3%), and <jats:italic>APC<\/jats:italic> (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 <jats:italic>GSTP1<\/jats:italic> (78.8%) and <jats:italic>RAR\u03b22<\/jats:italic> (34.6%). However, despite these epigenetic alterations none of these BNT patients developed prostate cancer, and those who underwent repeat mpMRI (<jats:italic>n<\/jats:italic>\u2009=\u20098) demonstrated either radiological regression or stability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Histologically benign PI\u2010RADS 4 and 5 lesions harbor prostate cancer\u2010associated epigenetic alterations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24255","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T17:48:53Z","timestamp":1634838533000},"page":"145-153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Histologically benign PI\u2010RADS 4 and 5 lesions contain cancer\u2010associated epigenetic 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