PTEN Protein Loss in Diagnostic Prostate Biopsies Is Associated with Gleason Score Upgrading in Radical Prostatectomy

Background/Objectives: Prostate needle biopsy often underestimates tumor aggressiveness due to limited tissue sampling, leading to Gleason score upgrading after radical prostatectomy (RP). Phosphatase and Tensin Homolog (PTEN) loss is an established tissue-based marker of adverse prostate cancer biology. This study evaluated whether reduced or absent PTEN immunoreactivity in diagnostic biopsies is associated with subsequent Gleason score and International Society of Urological Pathology (ISUP) Grade Group upgrading in RP specimens. Methods: This retrospective study included 85 prostate cancer patients who underwent multiparametric magnetic resonance imaging (mpMRI)-guided biopsy and subsequent RP. PTEN expression on biopsy samples was assessed via immunohistochemistry. Patients were stratified into PTEN-preserved (PTEN+, n = 75) and PTEN-deficient (PTEN−, n = 10) groups. Results: Upgrading occurred in 70% (7/10) of PTEN-deficient cases compared with 20% (15/75) of PTEN-preserved cases. This difference was statistically significant (two-sided Fisher’s exact p = 0.0024), with PTEN-deficient patients showing a 3.50-fold higher relative risk of upgrading (RR = 3.50, 95% CI: 1.91–6.43). Preoperative PSA levels (p = 0.91) and Prostate Imaging Reporting and Data System (PI-RADS) scores (p = 0.73) did not differ significantly between the groups. Conclusions: Reduced PTEN protein expression, as assessed by immunohistochemistry in prostate needle biopsies, was significantly associated with Gleason score/ISUP Grade Group upgrading at radical prostatectomy. PTEN immunohistochemistry warrants further evaluation as a potentially complementary tissue-based marker of biopsy undergrading. However, the observed unadjusted association does not establish PTEN immunoreactivity as an independent predictor of upgrading.