{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T21:29:49Z","timestamp":1781731789399,"version":"3.54.5"},"reference-count":11,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University\u2014Pleven, Bulgaria","award":["D7\/2024"],"award-info":[{"award-number":["D7\/2024"]}]},{"name":"Medical University\u2014Pleven, Bulgaria","award":["BG-RRP-2.004-0003"],"award-info":[{"award-number":["BG-RRP-2.004-0003"]}]},{"name":"European Union\u2014NextGenerationEU","award":["D7\/2024"],"award-info":[{"award-number":["D7\/2024"]}]},{"name":"European Union\u2014NextGenerationEU","award":["BG-RRP-2.004-0003"],"award-info":[{"award-number":["BG-RRP-2.004-0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: This study aimed to profile the molecular variants of muscle-invasive bladder cancer (MIBC) based on immunohistochemical analysis and to make a correlation with morphological characteristics in a series of 100 consecutive patients. Methods: A retrospective single-center study was conducted on 100 consecutive cases of MIBC (2021\u20132024). A selected immunohistochemical (IHC) panel (including CK5\/6, CK20, and p16) was applied in all cases to classify the tumors into known molecular variants (luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal\/squamous, neuroendocrine-like). Results: Seven molecular subtypes are identified: basal (33%), luminal papillary (24%), luminal unstable (16%), luminal non-specified (10%), basoluminal (double-positive) (9%), neuroendocrine-like (double-negative with neuroendocrine morphology) (6%), and stroma-rich (2%). This distribution largely matches published data (Consensus Classification and The Cancer Genome Atlas (TCGA)), with minor differences (e.g., a lower share of the stroma-rich variant). A strong correlation is found between the histological subtypes of some tumors and their molecular variant (\u03c72, p &lt; 0.001): for example, all cases of urothelial carcinoma with squamous differentiation are basal, micropapillary tumors are entirely luminal, and small-cell carcinomas are neuroendocrine-like. Conclusions: The results demonstrate that the morphological subtype of urothelial carcinoma largely predetermines the molecular profile. Combining classic histopathology with IHC-based profiling allows for a more complete characterization of the tumor and aids prognosis and personalized treatment in MIBC.<\/jats:p>","DOI":"10.3390\/medsci13030202","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T10:05:17Z","timestamp":1758535517000},"page":"202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunohistochemistry-Based Molecular Profiling of Muscle-Invasive Bladder Cancer: Analysis of 100 Consecutive Cases with Morphological Correlation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0154-7575","authenticated-orcid":false,"given":"Elitsa","family":"Kraevska","sequence":"first","affiliation":[{"name":"Department of Pathoanatomy, Faculty of Medicine, Medical University-Pleven, 5800 Pleven, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savelina","family":"Popovska","sequence":"additional","affiliation":[{"name":"Department of Pathoanatomy, Faculty of Medicine, Medical University-Pleven, 5800 Pleven, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Saginala, K., Barsouk, A., Aluru, J.S., Rawla, P., Padala, S.A., and Barsouk, A. (2020). Epidemiology of Bladder Cancer. Med. Sci., 8.","DOI":"10.3390\/medsci8010015"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41389-023-00489-9","article-title":"Biological differences underlying sex and gender disparities in bladder cancer: Current synopsis and future directions","volume":"12","author":"Doshi","year":"2023","journal-title":"Oncogenesis"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sanguedolce, F., Zanelli, M., Palicelli, A., Ascani, S., Zizzo, M., Cocco, G., Bj\u00f6rnebo, L., Lantz, A., Falagario, U.G., and Cormio, L. (2022). Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 1: General Issues and Marker Expression. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147819"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.eururo.2019.09.006","article-title":"A Consensus Molecular Classification of Muscle-invasive Bladder Cancer","volume":"77","author":"Kamoun","year":"2020","journal-title":"Eur. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sanguedolce, F., Zanelli, M., Palicelli, A., Ascani, S., Zizzo, M., Cocco, G., Bj\u00f6rnebo, L., Lantz, A., Landriscina, M., and Conteduca, V. (2022). Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 2: Subtypes and Divergent Differentiation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147844"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.humpath.2021.04.001","article-title":"Molecular pathology of urothelial carcinoma","volume":"113","author":"Cimadamore","year":"2021","journal-title":"Hum. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.cell.2017.09.007","article-title":"Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer","volume":"171","author":"Robertson","year":"2017","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.eururo.2022.07.002","article-title":"The 2022 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs-Part B: Prostate and Urinary Tract Tumors","volume":"82","author":"Netto","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.pathol.2020.09.004","article-title":"Urothelial carcinoma: Variant histology, molecular subtyping, and immunophenotyping significant for treatment outcomes","volume":"53","author":"Takahara","year":"2021","journal-title":"Pathology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nrurol.2017.125","article-title":"Characteristics and clinical significance of histological variants of bladder cancer","volume":"14","author":"Moschini","year":"2017","journal-title":"Nat. Rev. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.21037\/amj.2020.02.02","article-title":"The impact of histological variants on bladder cancer outcomes","volume":"5","author":"Processali","year":"2020","journal-title":"AME Med. J."}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/3\/202\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:57Z","timestamp":1760035617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/3\/202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":11,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["medsci13030202"],"URL":"https:\/\/doi.org\/10.3390\/medsci13030202","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,22]]}}}