Real-world landscape of PTEN protein expression and its relationships with HER2 and PSMA in Chinese hormone-sensitive prostate cancer.

Abstract

e17102 Background: This study aimed to characterize the prevalence of PTEN loss and explore its associations with HER2 and PSMA in a large Chinese hormone-sensitive prostate cancer (HSPC) cohort. Methods: This retrospective real-world cohort study included patients with hormone-sensitive prostate cancer diagnosed by prostate biopsy at Peking University First Hospital between 2021 and 2025. PTEN, HER2 and PSMA protein expression were assessed by immunohistochemistry (IHC). Clinicopathologic variables were collected, and statistical analyses were performed to characterize PTEN expression patterns and evaluate associations with clinical features and the expression of clinically actionable biomarkers. Results: A total of 1,080 patients with HSPC were retrospectively included in the final analysis. Baseline clinicopathologic characteristics of the study population are summarized in Table 1. Clinical T stage at diagnosis was predominantly cT2 (n = 781, 72.7%), followed by cT3a (n = 201, 18.7%), cT3b (n = 60, 5.6%), and cT4 disease (n = 32, 3.0%). PTEN protein expression assessed by immunohistochemistry was available in all patients (n = 1,080). PTEN-negative, low, moderate, and strong expression was identified in 46 (4.3%), 495 (45.8%), 282 (26.1%), and 257 (23.8%) cases, respectively. Spearman rank correlation analyses demonstrated that PTEN expression levels were not significantly associated with age, serum total PSA levels, clinical T stage (p = 0.347), ISUP grade group, or MRI PI-RADS score (p = 0.104).In contrast, PTEN loss was inversely associated with HER2 expression and PSMA expression, as reflected by a positive correlation between PTEN expression levels and HER2 (ρ = 0.222, p < 0.001) and PSMA expression (ρ = 0.808, p < 0.001). Conclusions: Absolute PTEN loss was rare ( < 5%) in the Chinese HSPC population, whereas low PTEN expression was more common. The complementary relationship between PTEN loss and HER2 and PSMA expression underscores molecular heterogeneity and may provide a reference for future precision treatment strategies in hormone-sensitive prostate cancer. Clinicopathologic characteristics according to PTEN expression status in HSPC. Variable PTEN=0 PTEN=1 PTEN=2 PTEN=3 P value Age, y 69(63-72) 69 (63-74) 69 (64.00-74) 70 (65-75) 0.066 PSA, ng/mL 14.82 (7.38-44.68) 14.95 (8.09-50.23) 18.48 (9.45-66.92) 14.51 (8.46-46.09) 0.510 ISUP group=1-2 18 (39.1%) 155 (31.3%) 99 (35.1%) 89 (34.6%) 0.372 ISUP group=3-5 28 (60.9%) 340 (68.7%) 183 (64.9%) 168 (65.4%) 0.372 HER2 status=0/1 5 (10.9%) 56 (11.3%) 43 (15.2%) 90 (35.0%) <0.001 HER2 status=2/3 41 (89.1%) 439 (88.7%) 239 (84.8%) 167 (65.0%) <0.001 PSMA status=0/1 3 (20.0%) 10 (3.8%) 42 (95.5%) 176 (89.3%) <0.001 PSMA status=2/3 12 (80.0%) 256 (96.2%) 2 (4.5%) 21 (10.7%) <0.001 Data are presented as median(Q1-Q3) for continuous variables and n(%) for categorical variables.