ABSTRACT Background Benign prostatic hyperplasia (BPH) encompasses a heterogeneous set of pathological processes that instigate lower urinary tract symptoms (LUTS). Using a mouse model of steroid hormone imbalance–induced lower urinary tract dysfunction, we identified luminal lipid‐laden foamy macrophages, although their presence and contribution to human pathology have not yet been established. The objective of this study was to determine whether luminal macrophages are associated with human BPH and to assess how lipid accumulation relates to underlying pathological features and clinical parameters. Methods Whole‐mount tissue sections from simple prostatectomy specimens and prostates from healthy donors were used to evaluate the association of luminal macrophages by immunohistochemistry and lipid content by Oil Red O staining. For a systematic assessment of inflammatory cells (CD45⁺ and CD68⁺), collagen content (Picrosirius Red), glandular proportion (H a glandular‐enriched, low‐immune phenotype; a large‐prostate subtype characterized by high lipid content and inflammation; and a macrophage‐enriched phenotype. Notably, the small stromal‐fibrotic subtype was enriched for patients receiving 5α‐reductase inhibitor therapy. Conclusions In summary, our findings identify luminal macrophages and lipid accumulation as previously underrecognized pathological features of BPH. Lipid accumulation is associated with prostatic inflammation and may represent a therapeutic target. Luminal macrophages may further contribute to disease progression, and comprehensive transcriptomic and proteomic characterization of these cells in human tissue will be essential to elucidate their pathological functions. Importantly, effective implementation of subtype‐informed BPH management will require improved biomarkers and imaging strategies to enable accurate disease stratification and personalized treatment selection.
Julianingsih et al. (Tue,) studied this question.