Font, AlbertDoménech, MontserratBenítez, RaquelRava, MartaMarqués, MiriamRamírez, José L.Pineda, SilviaDomínguez Rodríguez, MiriamGago, José L.Badal, JosepCarrato, CristinaLópez, HéctorQuer, AriadnaCastellano, DanielMalats i Riera, NúriaReal, Francisco X.2020-09-162020-09-162020Font 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/cancers120717842072-6694http://hdl.handle.net/10230/45290Background: 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.application/pdfeng© 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/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/cancers12071784Basal/squamous-like tumorsBladder cancerImmunohistochemistryMolecular taxonomyNeoadjuvant chemotherapyinfo:eu-repo/semantics/openAccess