Refining prostate cancer diagnosis: correlative analysis of Gleason scores and immunohistochemical markers

Distinguishing prostate cancer (PCa) from benign prostatic tissue can be challenging in equivocal cases. Gleason grading remains the gold standard, with immunohistochemical (IHC) markers such as androgen receptor (AR), prostate-specific antigen (PSA), and α-methylacyl-CoA racemase (P504S/AMACR) serving as established adjuncts. This study aimed to confirm their diagnostic utility in a retrospective Chinese cohort of PCa and benign controls (primarily benign prostatic hyperplasia [BPH]). This retrospective analysis included 147 patients (88 PCa, 59 BPH) evaluated between 2020 and 2024 at two Chinese institutions. Gleason scores were extracted from pathology reports. IHC for AR, PSA, P504S (AMACR), and hematopoietic cell kinase (HCK) was performed routinely when clinically indicated. AR staining (when available) was assessed exclusively in tumor cell nuclei, with positivity defined qualitatively by any discernible nuclear staining (typically >1% of cells, including weak intensity). Due to the retrospective design and routine practice, no uniform cutoff or re-scoring was applied. AR and PSA results were available in most cases, whereas P504S was assessed in a subset (40/88 PCa; 19/59 benign), typically diagnostically ambiguous samples. Marker positivity was compared between PCa and benign tissue and correlated with Gleason score components and patient age. AR and PSA positivity were significantly higher in PCa than benign tissue (AR: 25.0% vs. 8.5%, p=0.011; PSA: 40.9% vs. 20.3%, p=0.009), consistent with prior reports. The lower AR rate in PCa (25.0%) likely reflects routine clinical reporting variability and thresholds. In assessed subsets, P504S was positive in 100% (40/40) of PCa cases versus 26.3% (5/19) of benign cases (p<0.0001), aligning with its established sensitivity. AR positivity peaked in intermediate Gleason grades but declined in high-grade tumors, while PSA showed a modest increasing trend with grade. HCK was uniformly negative in all assessed cases, supporting its limited diagnostic relevance. No significant age association was observed with Gleason categories. This retrospective analysis corroborates the complementary roles of P504S (in assessed subsets), AR, and PSA as valuable IHC adjuncts to Gleason grading for evaluating prostate tissue, including differentiation from benign conditions such as BPH. HCK negativity further supports its deprioritization in diagnostic panels.