Expression of STAT3 and STAT6 in Men with Large Versus Small Prostates Undergoing Transurethral Resection of the Prostate

Background and Objectives: The factors driving variations in prostate size in patients with benign prostatic hyperplasia (BPH) remain unclear. We evaluated the differential expression of signal transducer and activator of transcription (STAT) 3 and 6 in patients with BPH and large versus small prostates. Materials and Methods: Among men who underwent transurethral resection of the prostate (TURP), we defined, with reference to the mean prostate volume (PV) reported for Korean men aged 70 years or older, a small-prostate group (PV ≤ 33 mL) and a large-prostate group (PV > 60 mL). Basic demographics, serum prostate-specific antigen (PSA) levels, International Prostate Symptom Score (IPSS), quality of life (QoL), PV, and preoperative uroflowmetry values were evaluated. Tissue sections were assessed by immunofluorescence staining under a confocal laser-scanning microscope and histologically classified into prostatic gland and stroma. Mean fluorescence intensities of STAT3 and STAT6 were quantified using an image analyser. Results: STAT3 immunoreactivity was consistently higher in the stroma than in the glandular compartment in both groups (paired difference 43.1, p < 0.001), with no difference between volume groups in any compartment. Stromal STAT6 immunoreactivity was higher in the small-prostate group (65.2 ± 14.7 vs. 56.5 ± 14.1; mean difference 8.7, 95% CI 0.2–17.3, p = 0.045), and the estimate was similar in mixed-effects and generalised estimating equation models accounting for within-patient clustering (p = 0.030 and p = 0.030). This exploratory difference did not remain significant after correction for six comparisons (Holm-adjusted p = 0.269), and its correlations with clinical variables were not significant after correction. No difference was detected in the glandular or nodular compartments. Conclusions: STAT3 immunoreactivity showed a consistent stromal predominance across both volume groups, whereas stromal STAT6 immunoreactivity was higher in men with small prostates. This exploratory association was consistent across analytical approaches but did not survive correction for multiple comparisons. Because total rather than phosphorylated protein was measured, these data localise a candidate signal to the stromal compartment rather than demonstrating pathway activation. Given experimental evidence linking STAT6 signalling to prostatic fibrosis, the finding defines a testable hypothesis for phospho-specific and histological studies of stromal remodelling in men with small prostates.