{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T06:55:03Z","timestamp":1781592903770,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K01DK127150"],"award-info":[{"award-number":["K01DK127150"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK139114"],"award-info":[{"award-number":["R01DK139114"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013965","name":"Eastern Virginia Medical School","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013965","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u2013induced lower urinary tract dysfunction, we identified luminal lipid\u2010laden 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole\u2010mount 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\u207a and CD68\u207a), collagen content (Picrosirius Red), glandular proportion (H&amp;E), and lipid accumulation, prostate tissues were obtained from patients undergoing holmium laser enucleation of the prostate (HoLEP). Clinical data, including IPSS and LURN symptom scores, were collected, and relevant clinical variables were extracted by chart review. Pathological subtypes were subsequently identified using unsupervised hierarchical clustering.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Lumens containing CD68\u207a macrophages were increased 6.2\u2010fold and 6.6\u2010fold in glandular nodules and internodular regions, respectively, compared with the transition zone of donors. Overall lipid content was also elevated by 2.8\u2010fold in glandular nodules relative to healthy transition zone tissue. In HoLEP specimens, lipid content showed positive correlations with glandular proportion, CD45\u207a and CD68\u207a cell abundance, prostate volume, and serum PSA, and negative correlations with collagen content and body mass index. Unsupervised hierarchical clustering of pathological features identified four distinct subtypes: a small, stromal\u2010fibrotic phenotype; a glandular\u2010enriched, low\u2010immune phenotype; a large\u2010prostate subtype characterized by high lipid content and inflammation; and a macrophage\u2010enriched phenotype. Notably, the small stromal\u2010fibrotic subtype was enriched for patients receiving 5\u03b1\u2010reductase inhibitor therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u2010informed BPH management will require improved biomarkers and imaging strategies to enable accurate disease stratification and personalized treatment selection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70195","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T18:05:53Z","timestamp":1779818753000},"page":"1157-1169","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid and Foam Cell Accumulation as Novel Pathological Features of Benign Prostatic Hyperplasia"],"prefix":"10.1002","volume":"86","author":[{"given":"Dita","family":"Julianingsih","sequence":"first","affiliation":[{"name":"Department of Biomedical and Translational Sciences Eastern Virginia Medical School at Old Dominion University Norfolk Virginia USA"},{"name":"Leroy T. Canoles Jr. Cancer Research Center Macon &amp; Joan Brock Virginia Health Sciences at Old Dominion University Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samara V.","family":"Silver","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences Eastern Virginia Medical School at Old Dominion University Norfolk Virginia USA"},{"name":"Leroy T. Canoles Jr. Cancer Research Center Macon &amp; Joan Brock Virginia Health Sciences at Old Dominion University Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaissa","family":"Horne","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences Eastern Virginia Medical School at Old Dominion University Norfolk Virginia USA"},{"name":"Leroy T. Canoles Jr. Cancer Research Center Macon &amp; Joan Brock Virginia Health Sciences at Old Dominion University Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasun","family":"Gunawardena","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences Eastern Virginia Medical School at Old Dominion University Norfolk Virginia USA"},{"name":"Leroy T. Canoles Jr. Cancer Research Center Macon &amp; Joan Brock Virginia Health Sciences at Old Dominion University Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences Eastern Virginia Medical School at Old Dominion University Norfolk Virginia USA"},{"name":"Leroy T. Canoles Jr. Cancer Research Center Macon &amp; Joan Brock Virginia Health Sciences at Old Dominion University Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Malewska","sequence":"additional","affiliation":[{"name":"Department of Urology UT Southwestern Medical Center Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Strand","sequence":"additional","affiliation":[{"name":"Department of Urology UT Southwestern Medical Center Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Nyalwidhe","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences Eastern Virginia Medical School at Old Dominion University Norfolk Virginia USA"},{"name":"Leroy T. Canoles Jr. Cancer Research Center Macon &amp; Joan Brock Virginia Health Sciences at Old Dominion University Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Sobol","sequence":"additional","affiliation":[{"name":"Department of Urology Eastern Virginia Medical School at Old Dominion University Norfolk Virginia USA"},{"name":"Urology of Virginia Suffolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9179-0575","authenticated-orcid":false,"given":"Petra","family":"Popovics","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Translational Sciences Eastern Virginia Medical School at Old Dominion University Norfolk Virginia USA"},{"name":"Leroy T. Canoles Jr. Cancer Research Center Macon &amp; Joan Brock Virginia Health Sciences at Old Dominion University Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"issue":"5","key":"e_1_2_8_2_1","first-page":"122","article-title":"BPH: Epidemiology and Comorbidities","volume":"12","author":"McVary K. T.","year":"2006","journal-title":"American Journal of Managed Care"},{"issue":"9","key":"e_1_2_8_3_1","first-page":"S3","article-title":"Benign Prostatic Hyperplasia: An Overview","volume":"7","author":"Roehrborn C. G.","year":"2005","journal-title":"Reviews in Urology"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","unstructured":"J. A.Rodriguez\u2010NievesandJ. 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