Biomedicines (Sep 2024)

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

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

DOI
https://doi.org/10.3390/biomedicines12092154
Journal volume & issue
Vol. 12, no. 9
p. 2154

Abstract

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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.

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