Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer

Meireles, Sara; Dias, Carolina; Martins, Diana; Marques, Ana; Dias, Nuno; Pacheco-Figueiredo, Luís; Silva, João; Silva, Carlos Martins; Barbosa, Miguel; Costa, Luís; Lopes, José Manuel; Soares, Paula

doi:10.3390/biomedicines12092154

Open AccessArticle

Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer

by

Sara Meireles

^{1,2,3,4,*,†}

,

Carolina Dias

^1,2,3,†

,

Diana Martins

^3,5,

Ana Marques

^3,5

,

Nuno Dias

^3,6,

Luís Pacheco-Figueiredo

^7,8,

João Silva

^3,6

,

Carlos Martins Silva

^1,3,6,

Miguel Barbosa

⁴,

Luís Costa

^9,10

,

José Manuel Lopes

^1,2,3,5,‡

and

Paula Soares

^1,2,3,‡

¹

Institute for Research and Innovation in Health (i3S), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal

²

Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal

³

Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal

⁴

Medical Oncology Department, Centro Hospitalar Universitário de São João (CHUSJ), Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal

⁵

Pathology Department, Centro Hospitalar Universitário de São João, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal

⁶

Urology Department, Centro Hospitalar Universitário de São João (CHUSJ), Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal

⁷

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal

⁸

Department of Urology, Trofa Saúde Private Hospitals, 4785-409 Trofa, Portugal

⁹

Medical Oncology Department, Centro Hospitalar Universitário Lisboa Norte, Avenida Professor Egas Moniz MB, 1649-028 Lisboa, Portugal

¹⁰

Institute of Molecular Medicine—João Lobo Antunes, Faculty of Medicine, University of Lisbon, Avenida Professor Egas Moniz MB, 1649-028 Lisboa, Portugal

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

These authors contributed equally to this work.

Biomedicines 2024, 12(9), 2154; https://doi.org/10.3390/biomedicines12092154

Submission received: 5 August 2024 / Revised: 9 September 2024 / Accepted: 14 September 2024 / Published: 23 September 2024

(This article belongs to the Special Issue Urothelial Carcinoma: Role of Biomarkers in Diagnosis, Prognosis and Treatment)

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Abstract

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–Meier 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% 1.508–8.453, p = 0.004) but with no impact in OS (HR 1.279, CI 95% 0.513–3.190, 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.

Keywords: upper tract urothelial carcinoma; molecular profiles; biomarkers; immunohistochemical stratification; bladder cancer

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MDPI and ACS Style

Meireles, S.; Dias, C.; Martins, D.; Marques, A.; Dias, N.; Pacheco-Figueiredo, L.; Silva, J.; Silva, C.M.; Barbosa, M.; Costa, L.; et al. Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer. Biomedicines 2024, 12, 2154. https://doi.org/10.3390/biomedicines12092154

AMA Style

Meireles S, Dias C, Martins D, Marques A, Dias N, Pacheco-Figueiredo L, Silva J, Silva CM, Barbosa M, Costa L, et al. Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer. Biomedicines. 2024; 12(9):2154. https://doi.org/10.3390/biomedicines12092154

Chicago/Turabian Style

Meireles, Sara, Carolina Dias, Diana Martins, Ana Marques, Nuno Dias, Luís Pacheco-Figueiredo, João Silva, Carlos Martins Silva, Miguel Barbosa, Luís Costa, and et al. 2024. "Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer" Biomedicines 12, no. 9: 2154. https://doi.org/10.3390/biomedicines12092154

APA Style

Meireles, S., Dias, C., Martins, D., Marques, A., Dias, N., Pacheco-Figueiredo, L., Silva, J., Silva, C. M., Barbosa, M., Costa, L., Lopes, J. M., & Soares, P. (2024). Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer. Biomedicines, 12(9), 2154. https://doi.org/10.3390/biomedicines12092154

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Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer

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