288 Expression Profiles of PSA, PSAP, and PSMA Across Metastatic Sites in Prostate Cancer: Implications for Immunohistochemical Interpretation

Introduction/Objective Accurate immunohistochemical identification of prostatic origin in metastatic tumors is essential for guiding treatment decisions. While PSA remains the most widely used marker, PSAP and PSMA are increasingly employed in challenging or dedifferentiated cases. This study evaluates the expression patterns of these markers across various metastatic sites to inform their diagnostic utility. Methods/Case Report A retrospective analysis of 22 metastatic prostate cancer cases diagnosed at our institution from 2021 to 2024 was performed. Formalin-fixed, paraffin-embedded tissue sections from metastatic sites — including bone, liver, lung, lymph node, pleura, skin, and bladder — were subjected to immunohistochemical staining for PSA, PSAP, and PSMA. Each was scored using an immunoreactive score (IRS): 0 (negative), 1 (1–10%), 2 (11–50%), 3 (51–80%), and 4 (>80%). Marker distributions were visualized using box plots. Pearson correlation analysis assessed inter-marker relationships, and site-specific trends were qualitatively evaluated. Results All three markers were expressed across all metastatic sites. Bone and liver metastases demonstrated diffuse (IRS 2–4) expression of PSA, PSAP, and PSMA in over 80% of cases. Lung and lymph node sites exhibited more variability, with one lymph node case negative for PSMA and one lung case showing low PSMA expression (IRS 1). Bladder, pleura, and skin cases (n = 1 each) showed uniformly high expression across all markers. PSA and PSAP demonstrated more consistent expression than PSMA. Correlation analysis revealed moderate co-expression between PSA and PSAP (r = 0.49) and between PSAP and PSMA (r = 0.50), while PSA and PSMA showed a weaker correlation (r = 0.25). Conclusion PSA, PSAP, and PSMA are robust markers across metastatic prostate cancer sites. While all three are diagnostically valuable, PSAP and PSA showed the most consistent, site-independent expression. PSMA adds complementary value, particularly in cases with discordant staining or in sites such as lymph nodes and lungs, where expression may be more variable. These findings support the routine use of all three markers in immunohistochemical panels to improve diagnostic accuracy in metastatic prostate cancer.