Risk-Stratified Gleason Upgrading in ISUP Grade Group 1 Prostate Cancer: Combined Analysis of TMPRSS2-ERG, PTEN, Ki-67, and MRI-Derived Apparent Diffusion Coefficient Values.

OBJECTIVE: To evaluate molecular, immunohistochemical, and radiological parameters associated with pathological upgrading in patients with ISUP Grade Group 1 (GG1) prostate cancer who underwent radical prostatectomy (RP).

METHODS: A total of 106 patients diagnosed with ISUP GG1 prostate adenocarcinoma via needle biopsy and treated with RP between 2012 and 2022 were retrospectively analyzed. Based on final pathology, patients were categorized into No Upgrade, Low-risk Upgrade, and High-risk Upgrade groups. Biopsy specimens were evaluated for PTEN, ERG, and Ki-67 expression and TMPRSS2-ERG gene fusion status, while radiological parameters, including PI-RADS v2.1 scores and ADC values (ADCtumor and ADCratio), were assessed based on preoperative multiparametric MRI.

RESULTS: TMPRSS2-ERG fusion positivity and elevated ERG expression were significantly more common in the High-risk Upgrade group (p < 0.01 and p = 0.04, respectively). PI-RADS scores showed a stepwise increase, and ADCtumor values decreased across risk groups (p = 0.01 and p = 0.03). No significant differences were observed for PTEN loss, Ki-67 index, or ADCratio.

CONCLUSION: Certain immunohistochemical, radiological, and molecular parameters may be predictive of pathological upgrading in GG1 prostate cancer. Incorporation of these biomarkers into diagnostic evaluation and treatment planning may aid in refining risk stratification and avoiding overtreatment in clinically indolent cases. Although ADCtumor values were significantly associated with upgrading, their correlation with molecular markers such as PTEN, ERG, Ki-67, and TMPRSS2-ERG fusion were not statistically significant.

TRIAL REGISTRATION: Project No: 2023TIPF001.