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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.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.issn 2072-6694
dc.identifier.uri http://hdl.handle.net/10230/45290
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.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.uri http://creativecommons.org/licenses/by/4.0/
dc.title Immunohistochemistry-based taxonomical classification of bladder cancer predicts response to neoadjuvant chemotherapy
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3390/cancers12071784
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.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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