Immunohistochemistry-based taxonomical classification of bladder cancer predicts response to neoadjuvant chemotherapy

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• dc.contributor.author Font, Albert
• dc.contributor.author Doménech, Montserrat
• dc.contributor.author Benítez, Raquel
• dc.contributor.author Rava, Marta
• dc.contributor.author Marqués, Miriam
• dc.contributor.author Ramírez, José L.
• dc.contributor.author Pineda, Silvia
• dc.contributor.author Domínguez Rodríguez, Miriam
• dc.contributor.author Gago, José L.
• dc.contributor.author Badal, Josep
• dc.contributor.author Carrato, Cristina
• dc.contributor.author López, Héctor
• dc.contributor.author Quer, Ariadna
• dc.contributor.author Castellano, Daniel
• dc.contributor.author Malats i Riera, Núria
• dc.contributor.author Real, Francisco X.
• dc.date.accessioned 2020-09-16T06:25:05Z
• dc.date.available 2020-09-16T06:25:05Z
• dc.date.issued 2020
• dc.description.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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Font A, Domènech M, Benítez R, Rava M, Marqués M, Ramírez JL, Pineda S, Domínguez-Rodríguez S, Gago JL, Badal J, Carrato C, López H, Quer A, Castellano D, Malats N, Real FX. Immunohistochemistry-based taxonomical classification of bladder cancer predicts response to neoadjuvant chemotherapy. Cancers (Basel). 2020; 12(7):1784. DOI: 10.3390/cancers12071784
• dc.identifier.doi http://dx.doi.org/10.3390/cancers12071784
• dc.identifier.issn 2072-6694
• dc.identifier.uri http://hdl.handle.net/10230/45290
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Cancers (Basel). 2020; 12(7):1784
• dc.rights © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Basal/squamous-like tumors
• dc.subject.keyword Bladder cancer
• dc.subject.keyword Immunohistochemistry
• dc.subject.keyword Molecular taxonomy
• dc.subject.keyword Neoadjuvant chemotherapy
• dc.title Immunohistochemistry-based taxonomical classification of bladder cancer predicts response to neoadjuvant chemotherapy
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion