TERT expression in human prostate tissue reveals a potential molecular switch in benign prostatic hyperplasia progression.

PURPOSE: Benign prostatic hyperplasia (BPH) is a leading cause of voiding symptoms in aging men. Telomerase reverse transcriptase (TERT), a key regulator of cellular senescence and tissue remodeling, has not been systematically examined in human voiding symptoms, though genome-wide association studies suggested a role in genetic and sporadic BPH.

METHODS

Prostate tissues from patients undergoing laser enucleation for BPH were analyzed by RT-PCR. Clinical parameters were compared between TERT-positive and -negative patients. TERT expression in laser-enucleated tissues was tested for correlation with contractile smooth muscle receptors and the proliferation marker Ki67, and compared to tissues from radical prostatectomy for prostate cancer.

RESULTS

In a cohort of 100 patients undergoing laser enucleation of the prostate, we detected prostatic TERT mRNA in 81% of samples. Patients with TERT-positive tissues displayed clinically relevant higher symptom scores (22.5 vs. 17.4, p = 0.0407), and more pronounced post-void residual urine (80 vs. 142 ml). Prostate volume and free PSA showed no relationship with TERT expression. TERT expression correlated with expression of α1A-adrenoceptors (p < 0.0001), endothelin receptor A (p < 0.0001) and B (p < 0.0001), thromboxane receptor (p < 0.0001), thromboxane synthase (p = 0.0050) and Ki67 (p = 0.0181). TERT expression was 460-fold higher (p = 0.0015) in laser-enucleated than in periurethral prostatectomized tissues.

CONCLUSIONS

TERT expression associates with higher symptom severity in laser-enucleated BPH patients, and correlates with targets imparting drug resistance. We propose that TERT acts as a molecular switch, marking a clinically more severe BPH phenotype. This finding raises the possibility of targeted intervention in BPH patients with TERT-driven pathology.