Immunohistochemistry-Based Taxonomical Classification of Bladder Cancer Predicts Response to Neoadjuvant Chemotherapy
Font, Albert (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Domènech, Montserrat (Medical Oncology Department, Fundació Althaia, 08243 Manresa, Spain)
Benítez, Raquel (Centro Nacional de Investigaciones Oncológicas)
Rava, Marta (Centro Nacional de Investigaciones Oncológicas)
Marqués, Miriam (Centro Nacional de Investigaciones Oncológicas)
Ramirez, Jose Luis (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Pineda, Silvia (Centro Nacional de Investigaciones Oncológicas)
Domínguez-Rodríguez, Sara (Centro Nacional de Investigaciones Oncológicas)
Gago Ramos, José Luis (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Badal Lafulla, Josep (Pathology Department, Fundació Althaia, 08243 Manresa, Spain)
Carrato, Cristina (Universitat Autònoma de Barcelona. Facultat de Medicina)
López, Héctor (Urology Department, Fundació Althaia, 08243 Manresa, Spain)
Quer, Ariadna (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Castellano, Daniel (Hospital Universitario 12 de Octubre (Madrid))
Malats, Núria (Centro de Investigación Biomédica en Red de Cáncer)
Real, Francisco X. (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)

Date:	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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Bladder cancer ; Neoadjuvant chemotherapy ; Molecular taxonomy ; Immunohistochemistry ; Basal/squamous-like tumors
Published in:	Cancers, Vol. 12 (july 2020) , ISSN 2072-6694

DOI: 10.3390/cancers12071784
PMID: 32635360

13 p, 1.1 MB

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