{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T02:50:04Z","timestamp":1774579804264,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institute for Research and Innovation in Health Sciences","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678"]}]},{"name":"Porto Comprehensive Cancer Center","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"Porto Comprehensive Cancer Center","award":["NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Background: Molecular profiling in upper tract urothelial carcinoma (UTUC) with synchronous or metachronous urothelial bladder cancer (UBC) is scarce. We intended to assess immunohistochemical (IHC) and genetic differences between UTUC-only and UTUC with synchronous or metachronous UBC (UTUC + UBC) and evaluate the effect of subsequent UBC on the outcome of UTUC patients stratified by luminal-basal subtypes. Methods: A retrospective cohort of UTUC was divided into UTUC-only (n = 71) and UTUC + UBC (n = 43). 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 and Cox regression analyses estimated the effect of clinicopathological variables and molecular profiles on progression-free survival (PFS) and overall survival (OS) of UTUC patients. Results: No meaningful differences were detected among both subgroups according to luminal-basal stratification and genetic analysis. UTUC + UBC was independently associated with a worse PFS when stratified by luminal-basal phenotype (HR 3.570, CI 95% 1.508\u20138.453, p = 0.004) but with no impact in OS (HR 1.279, CI 95% 0.513\u20133.190, p = 0.597). Conclusions: This study reveals that both subgroups exhibited equivalent genomic features and luminal-basal subtypes. The involvement of the bladder relates to shorter PFS but does not seem to influence the survival outcome of UTUC, independently of the IHC phenotype.<\/jats:p>","DOI":"10.3390\/biomedicines12092154","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T09:15:07Z","timestamp":1727082907000},"page":"2154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer"],"prefix":"10.3390","volume":"12","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":"Diana","family":"Martins","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, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3100-8323","authenticated-orcid":false,"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, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Nuno","family":"Dias","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"}]},{"given":"Lu\u00eds","family":"Pacheco-Figueiredo","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"Department of Urology, Trofa Sa\u00fade Private Hospitals, 4785-409 Trofa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6725-5767","authenticated-orcid":false,"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"}]},{"given":"Carlos Martins","family":"Silva","sequence":"additional","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"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"}]},{"given":"Miguel","family":"Barbosa","sequence":"additional","affiliation":[{"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\/0000-0002-4782-7318","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\u2014Jo\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, 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":[[2024,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.ccell.2021.05.004","article-title":"Molecular subtypes of upper tract urothelial cancer: Setting the stage for precision therapy","volume":"39","author":"McConkey","year":"2021","journal-title":"Cancer Cell."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","unstructured":"Marzouka, N.A., Eriksson, P., Rovira, C., Liedberg, F., Sj\u00f6dahl, G., and H\u00f6glund, M. (2018). A validation and extended description of the Lund taxonomy for urothelial carcinoma using the TCGA cohort. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-22126-x"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2014). Comprehensive molecular characterization of urothelial bladder carcinoma. Nature, 507, 315\u2013322.","DOI":"10.1038\/nature12965"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/path.4886","article-title":"Molecular classification of urothelial carcinoma: Global mRNA classification versus tumour-cell phenotype classification","volume":"242","author":"Eriksson","year":"2017","journal-title":"J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1093\/jnci\/djx243","article-title":"Prognostic Power of a Tumor Differentiation Gene Signature for Bladder Urothelial Carcinomas","volume":"110","author":"Mo","year":"2018","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ccell.2016.05.004","article-title":"Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma","volume":"30","author":"Hedegaard","year":"2016","journal-title":"Cancer Cell."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.juro.2012.05.079","article-title":"Urothelial carcinoma of the bladder and the upper tract: Disparate twins","volume":"4","author":"Green","year":"2013","journal-title":"J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.ccell.2021.05.008","article-title":"Molecular classification and diagnostics of upper urinary tract urothelial carcinoma","volume":"39","author":"Fujii","year":"2021","journal-title":"Cancer Cell."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.eururo.2015.07.039","article-title":"Genomic Characterization of Upper Tract Urothelial Carcinoma","volume":"68","author":"Sfakianos","year":"2015","journal-title":"Eur. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.eururo.2017.05.048","article-title":"Comprehensive Genomic Characterization of Upper Tract Urothelial Carcinoma","volume":"72","author":"Moss","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.tranon.2017.10.008","article-title":"Molecular Characterization of Urothelial Carcinoma of the Bladder and Upper Urinary Tract","volume":"11","author":"Lee","year":"2018","journal-title":"Transl. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1158\/1078-0432.CCR-18-2039","article-title":"Clonal Relatedness and Mutational Differences between Upper Tract and Bladder Urothelial Carcinoma","volume":"25","author":"Audenet","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1097\/JU.0000000000001788","article-title":"Expression Analysis of Same-Patient Metachronous and Synchronous Upper Tract and Bladder Urothelial Carcinoma","volume":"206","author":"Petros","year":"2021","journal-title":"J. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1158\/1078-0432.CCR-12-0077-T","article-title":"A molecular taxonomy for urothelial carcinoma","volume":"18","author":"Sjodahl","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1309\/AJCP5UAFMSA9ZQBZ","article-title":"Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: A useful immunomarker for breast and urothelial carcinomas","volume":"138","author":"Liu","year":"2012","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/his.13225","article-title":"p53 immunohistochemistry in high-grade urothelial carcinoma of the bladder is prognostically significant","volume":"71","author":"Hodgson","year":"2017","journal-title":"Histopathology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Meireles, S., Dias, N., Martins, D., Dias, C., Gon\u00e7alves, M., Silva, J., Silva, C.M., Oliveira, P.D., Soares, P., and Lopes, J.M. (2023). Prognostic Value of Bladder Involvement in the Outcome of Upper Tract Urothelial Carcinoma. Diagnostics, 13.","DOI":"10.3390\/diagnostics13010153"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","unstructured":"Wang, C.C., Tsai, Y.C., and Jeng, Y.M. (2019). Biological significance of GATA3, cytokeratin 20, cytokeratin 5\/6 and p53 expression in muscle-invasive bladder cancer. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221785"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sikic, D., Keck, B., Wach, S., Taubert, H., Wullich, B., Goebell, P.J., Kahlmeyer, A., Olbert, P., Isfort, P., and Nimphius, W. (2017). Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179602"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ebiom.2016.08.036","article-title":"Meta-Analysis of the Luminal and Basal Subtypes of Bladder Cancer and the Identification of Signature Immunohistochemical Markers for Clinical Use","volume":"12","author":"Dadhania","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Guo, C.C., Bondaruk, J., Yao, H., Wang, Z., Zhang, L., Lee, S., Lee, J.G., Cogdell, D., Zhang, M., and Yang, G. (2020). Assessment of Luminal and Basal Phenotypes in Bladder Cancer. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-66747-7"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Koll, F.J., Schwarz, A., Kollermann, J., Banek, S., Kluth, L., Wittler, C., Bankov, K., Doring, C., Becker, N., and Chun, F.K.H. (2022). CK5\/6 and GATA3 defined phenotypes of muscle-invasive bladder cancer: Impact in adjuvant chemotherapy and molecular subtyping of negative cases. Front. Med., 16.","DOI":"10.3389\/fmed.2022.875142"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3110","DOI":"10.1073\/pnas.1318376111","article-title":"Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology","volume":"111","author":"Damrauer","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ccr.2014.01.009","article-title":"Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy","volume":"25","author":"Choi","year":"2014","journal-title":"Cancer Cell."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lindgren, D., Sj\u00f6dahl, G., Lauss, M., Staaf, J., Chebil, G., L\u00f6vgren, K., Gudjonsson, S., Liedberg, F., Patschan, O., and M\u00e5nsson, W. (2012). Integrated genomic and gene expression profiling identifies two major genomic circuits in urothelial carcinoma. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038863"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.eururo.2008.06.013","article-title":"FGFR3 mutations indicate better survival in invasive upper urinary tract and bladder tumours","volume":"55","author":"Zwarthoff","year":"2009","journal-title":"Eur. Urol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11934-015-0566-y","article-title":"Prognostic Genetic Signatures in Upper Tract Urothelial Carcinoma","volume":"17","author":"Li","year":"2016","journal-title":"Curr. Urol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kompier, L.C., Lurkin, I., van der Aa, M.N., van Rhijn, B.W., van der Kwast, T.H., and Zwarthoff, E.C. (2010). FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013821"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1158\/1078-0432.CCR-14-2329","article-title":"Targeting FGFR Signaling in Cancer","volume":"21","author":"Touat","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.2217\/fon-2016-0042","article-title":"A place for precision medicine in bladder cancer: Targeting the FGFRs","volume":"12","author":"Tomlinson","year":"2016","journal-title":"Future Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12428","DOI":"10.18632\/oncotarget.2660","article-title":"TERT promoter mutations are associated with distant metastases in upper tract urothelial carcinomas and serve as urinary biomarkers detected by a sensitive castPCR","volume":"5","author":"Wang","year":"2014","journal-title":"Oncotarget"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6021","DOI":"10.1073\/pnas.1303607110","article-title":"TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal","volume":"110","author":"Killela","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.eururo.2013.08.052","article-title":"Telomerase reverse transcriptase promoter mutations in bladder cancer: High frequency across stages, detection in urine, and lack of association with outcome","volume":"65","author":"Allory","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109.e1","DOI":"10.1016\/j.urolonc.2021.08.019","article-title":"Differences in genomic profile of high-grade urothelial carcinoma according to tumor location","volume":"40","author":"Park","year":"2022","journal-title":"Urol. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.euf.2020.08.001","article-title":"Comprehensive Genomic Profiling of Upper-tract and Bladder Urothelial Carcinoma","volume":"7","author":"Necchi","year":"2021","journal-title":"Eur. Urol. Focus."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1080\/14789450.2020.1845654","article-title":"Multiomic analysis of cytokines in immuno-oncology","volume":"17","author":"Jurisic","year":"2020","journal-title":"Expert Rev. Proteom."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Batista, R., Lima, L., Vinagre, J., Pinto, V., Lyra, J., M\u00e1ximo, V., Santos, L., and Soares, P. (2020). TERT Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer Patients. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030947"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sanford, T., Porten, S., and Meng, M.V. (2015). Molecular Analysis of Upper Tract and Bladder Urothelial Carcinoma: Results from a Microarray Comparison. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137141"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.eururo.2015.02.021","article-title":"A Molecular Pathologic Framework for Risk Stratification of Stage T1 Urothelial Carcinoma","volume":"68","author":"Patschan","year":"2015","journal-title":"Eur. Urol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/modpathol.3880241","article-title":"Relationship of cytokeratin 20 and CD44 protein expression with WHO\/ISUP grade in pTa and pT1 papillary urothelial neoplasia","volume":"13","author":"Desai","year":"2000","journal-title":"Mod. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1097\/JU.0000000000000422","article-title":"Impact of Previous, Simultaneous or Subsequent Bladder Cancer on Prognosis after Radical Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma","volume":"202","author":"Kuroiwa","year":"2019","journal-title":"J. Urol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1097\/01.ju.0000144505.40915.98","article-title":"Bladder cancer as a prognostic factor for upper tract transitional cell carcinoma","volume":"172","author":"Mullerad","year":"2004","journal-title":"J. Urol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.eururo.2013.12.007","article-title":"A new proposal to risk stratify urothelial carcinomas of the upper urinary tract (UTUCs) in a predefinitive treatment setting: Low-risk versus high-risk UTUCs","volume":"66","author":"Colin","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wu, J., Xu, P.H., Luo, W.J., Dai, B., Shen, Y.J., Ye, D.W., Wang, Y.C., and Zhu, Y.P. (2021). Intravesical Recurrence After Radical Nephroureterectomy of Upper Urinary Tract Urothelial Carcinoma: A Large Population-Based Investigation of Clinicopathologic Characteristics and Survival Outcomes. Front. Surg., 8.","DOI":"10.3389\/fsurg.2021.590448"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ijsu.2020.02.015","article-title":"Risk factors and oncological outcome for intravesical recurrence in organ-confined upper urinary tract urothelial carcinoma patients after radical nephroureterectomy: A propensity score-matched case control study","volume":"76","author":"Jiang","year":"2020","journal-title":"Int. J. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.aju.2017.03.006","article-title":"Risk factors and prognosis of intravesical recurrence after surgical management of upper tract urothelial carcinoma: A 30-year single centre experience","volume":"15","author":"Elawdy","year":"2017","journal-title":"Arab. J. Urol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e1055","DOI":"10.1016\/j.clgc.2017.07.009","article-title":"Predictors for Intravesical Recurrence Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A National Multicenter Analysis","volume":"15","author":"Lee","year":"2017","journal-title":"Clin. Genitourin. Cancer"}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/12\/9\/2154\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:00:24Z","timestamp":1760112024000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/12\/9\/2154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,23]]},"references-count":50,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["biomedicines12092154"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines12092154","relation":{},"ISSN":["2227-9059"],"issn-type":[{"value":"2227-9059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,23]]}}}