The Role of p300 and TMPRSS2 in Prostate Cancer: Immunohistochemical Perspectives and Gleason Correlations

Transmembrane protease, serine 2 (TMPRSS2), and E1A-associated protein (p300) are important factors in prostate cancer (PCa) pathogenesis, playing significant roles in androgen receptor (AR) signaling and tumor progression. Despite their established role in PCa biology, their immunohistochemical alterations across different Gleason patterns and histological grades remain unclear. This experimental study aimed to assess TMPRSS2 and p300 expression in non-malignant and cancerous prostate tissues, correlating their localization and intensity with Gleason scores and tumor aggressiveness.

A total of 58 paraffin-embedded prostate adenocarcinoma (PRAD) tissue sections from male patients who underwent radical prostatectomy, including low- and high-grade tumors and high-grade prostatic intraepithelial neoplasia (HGPIN), were analyzed. Immunohistochemistry (IHC) for TMPRSS2 and p300 was performed. Two independent pathologists conducted H-score assessments with complete interobserver concordance, evaluating staining intensity, localization, and expression patterns, correlating findings with Gleason scores and cancer stage.

TMPRSS2 and p300 exhibited variable expression levels across all tissue samples. While TMPRSS2 expression increased in aggressive tumors, its staining intensity did not change significantly across different Gleason grades. p300 over-expression was significantly associated with aggressive tumors, particularly Gleason pattern 5 (p=0.011). High-grade tumors [Gleason ≥7(4+3)] demonstrated higher p300 expression compared to low-grade tumors [Gleason ≤7(3+4)], with minimal staining observed in Gleason score 6.

Expression patterns of TMPRSS2 and p300 correlate with PCa aggressiveness. These findings support the growing evidence suggesting their potential role as prognostic markers and therapeutic targets. The implementation of well-designed studies on a larger scale is of utmost importance, to draw safer conclusions.