{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T14:55:32Z","timestamp":1774536932559,"version":"3.50.1"},"reference-count":21,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRR\u2014Plano de Recupera\u00e7\u00e3o e Resili\u00eancia e pelos Fundos Europeus NextGenerationEU","award":["2022-C05IO101-02"],"award-info":[{"award-number":["2022-C05IO101-02"]}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["LA\/P\/0070\/2020"],"award-info":[{"award-number":["LA\/P\/0070\/2020"]}]},{"name":"The Porto Comprehensive Cancer Center\u201d\u2014Cons\u00f3rcio PORTO.CCC\u2014Porto. Comprehensive Cancer Center Raquel Seruca\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/02kcc1z29"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The features of patients with multiple urothelial tumors remain to be elucidated. We intend to differentiate primary upper tract urothelial carcinoma with synchronous urothelial bladder cancer (UTUC + sUBC) and UTUC with metachronous UBC (UTUC + mUBC) cases to determine whether these temporal patterns reflect biologically distinct processes. A subgroup analysis of a retrospective cohort of UTUC (n = 114) was performed comparing UTUC + sUBC (n = 14) with UTUC + mUBC (n = 29). IHC expression of cytokeratin 5\/6 (CK5\/6), CK20, GATA3, and p53 was evaluated to assess relevant subtypes. Genetic characterization comprised TERTp, FGFR3, RAS, and TP53 status. Kaplan\u2013Meier analyses estimated the progression-free survival (PFS) and overall survival (OS) of both UTUC subgroups, and the log-rank test was used to assess differences between subgroups. Our study reveals no significant differences in phenotype or genomic profile between synchronous and metachronous UTUC-UBC cases (p &gt; 0.05). Nevertheless, patients with synchronous UBC revealed significantly worse outcomes in PFS (2y-PFS 23.1% vs. 52.1%, p = 0.029) and OS (2y-OS 40.4% vs. 84.4%, p = 0.016) than those with metachronous disease. These discrepancies could arise from as yet-uncharacterized molecular features or microenvironmental influences.<\/jats:p>","DOI":"10.3390\/cimb48040345","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:37:15Z","timestamp":1774532235000},"page":"345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differentiating Upper Tract Urothelial Carcinoma with Synchronous or Metachronous Bladder Cancer"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9861-7986","authenticated-orcid":false,"given":"Sara","family":"Meireles","sequence":"first","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Medical Oncology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2884-0055","authenticated-orcid":false,"given":"Carolina","family":"Dias","sequence":"additional","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Ana","family":"Marques","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Pathology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Jo\u00e3o","family":"Silva","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Urology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4782-7318","authenticated-orcid":false,"given":"Lu\u00eds","family":"Costa","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Centro Hospitalar Universit\u00e1rio Lisboa Norte, Avenida Professor Egas Moniz MB, 1649-028 Lisboa, Portugal"},{"name":"Institute of Molecular Medicine Jo\u00e3o Lobo Antunes, Faculty of Medicine, University of Lisbon, Avenida Professor Egas Moniz MB, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8597-3474","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"Lopes","sequence":"additional","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Pathology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9607-6998","authenticated-orcid":false,"given":"Paula","family":"Soares","sequence":"additional","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. 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