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Immunohistochemistry-Based Molecular Subtyping in Muscle-Invasive Bladder Cancer: Predicting Response to Neoadjuvant

Luis Pérez-Bartivas1,2,3, Fernando Leiva-Cepas2,3,4,5, David Ponferrada1,2,3

  • 1Medical Oncology Department, Reina Sofía University Hospital, 14004 Cordoba, Spain.

Archivos Espanoles De Urologia
|July 13, 2026
PubMed
Summary

The luminal subtype of muscle-invasive bladder cancer (MIBC) shows better survival outcomes and response to neoadjuvant chemotherapy compared to double-positive tumors. This classification, based on GATA3 and CK5/6 expression, may guide treatment decisions.

Keywords:
bladder cancerimmunohistochemistrymolecular subtypeneoadjuvant chemotherapyurothelial carcinoma

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Area of Science:

  • Oncology
  • Pathology
  • Molecular Biology

Background:

  • Muscle-invasive bladder cancer (MIBC) exhibits varied responses to neoadjuvant chemotherapy.
  • Molecular subtypes, particularly luminal and basal, are recognized in MIBC.
  • GATA binding protein 3 (GATA3) and cytokeratin 5/6 (CK5/6) immunohistochemistry are key markers for MIBC subtyping.

Purpose of the Study:

  • To investigate the association between MIBC molecular subtypes (luminal, basal, double-positive, double-negative) defined by GATA3 and CK5/6 expression.
  • To evaluate the impact of these subtypes on treatment response to neoadjuvant chemotherapy.

Main Methods:

  • Retrospective analysis of 69 nonmetastatic MIBC patients treated with cisplatin-based neoadjuvant chemotherapy.
  • Tumor classification into luminal (GATA3+, CK5/6-), basal (GATA3-, CK5/6+), double-positive (GATA3+, CK5/6+), and double-negative (GATA3-, CK5/6-) subtypes.
  • Kaplan-Meier curves, log-rank tests, and chi-squared tests were used to analyze overall survival (OS), disease-free survival (DFS), and pathological response.

Main Results:

  • Luminal tumors (13/69) demonstrated significantly higher five-year DFS (91.7%) and OS (100%) compared to double-positive tumors (50/69) (DFS: 50.7%, OS: 60.5%).
  • Higher rates of pathological complete response (ypT0) (53.8% vs. 30.0%) and tumor downstaging (
  • Basal and double-negative subtypes were excluded due to low patient numbers.

Conclusions:

  • The luminal subtype of MIBC is associated with superior disease-free survival and overall survival following neoadjuvant chemotherapy compared to the double-positive subtype.
  • Luminal tumors showed a trend towards better pathological complete response and tumor downstaging.
  • GATA3 and CK5/6 expression may serve as predictive biomarkers for neoadjuvant chemotherapy response in MIBC.