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Immunohistochemistry-Based Taxonomical Classification of Bladder Cancer Predicts Response to Neoadjuvant Chemotherapy.

Authors :
Font, Albert
Domènech, Montserrat
Benítez, Raquel
Rava, Marta
Marqués, Miriam
Ramírez, José L.
Pineda, Silvia
Domínguez-Rodríguez, Sara
Gago, José L.
Badal, Josep
Carrato, Cristina
López, Héctor
Quer, Ariadna
Castellano, Daniel
Malats, Núria
Real, Francisco X.
Source :
Cancers; Jul2020, Vol. 12 Issue 7, p1784, 1p
Publication Year :
2020

Abstract

Background: Platinum-based neoadjuvant chemotherapy (NAC) increases the survival of patients with organ-confined urothelial bladder cancer (UBC). In retrospective studies, patients with basal/squamous (BASQ)-like tumors present with more advanced disease and have worse prognosis. Transcriptomics-defined tumor subtypes are associated with response to NAC. Aim: To investigate whether immunohistochemical (IHC) subtyping predicts NAC response. Methods: Patients with muscle-invasive UBC having received platinum-based NAC were identified. Tissue microarrays were used to type tumors for KRT5/6, KRT14, GATA3, and FOXA1. Outcomes: progression-free survival and disease-specific survival; univariable and multivariate Cox regression models were applied. Results: We found a very high concordance between mRNA and protein expression. Using IHC-based hierarchical clustering, we classified 126 tumors in three subgroups: BASQ-like (FOXA1/GATA3 low; KRT5/6/14 high), Luminal-like (FOXA1/GATA3 high; KRT5/6/14 low), and mixed-cluster (FOXA1/GATA3 high; KRT5/6 high; KRT14 low). Applying multivariable analyses, patients with BASQ-like tumors were more likely to achieve a pathological response to NAC (OR 3.96; p = 0.017). The clinical benefit appeared reflected in the lack of significant survival differences between patients with BASQ-like and luminal tumors. Conclusions: Patients with BASQ-like tumors—identified through simple and robust IHC—have a higher likelihood of undergoing a pathological complete response to NAC. Prospective validation is required. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20726694
Volume :
12
Issue :
7
Database :
Complementary Index
Journal :
Cancers
Publication Type :
Academic Journal
Accession number :
144873968
Full Text :
https://doi.org/10.3390/cancers12071784