Font, AlbertDomènech, MontserratRaquel Benítez, RaquelRava, MartaMarqués, MiriamRamírez, José L.Pineda Sanjuan, SilviaDomínguez Rodríguez, SaraGago, José L.Badal, JosepCarrato, CristinaLópez, HéctorQuer, AriadnaCastellano Gauna, Daniel ErnestoMalats, NúriaReal, Francisco X.Mok, Samuel C.2024-01-302024-01-302020-07-03Font A, Domènech M, Benítez R, Rava M, Marqués M, Ramírez JL, et al. Immunohistochemistry-Based Taxonomical Classification of Bladder Cancer Predicts Response to Neoadjuvant Chemotherapy. Cancers 2020;12:1784. https://doi.org/10.3390/cancers12071784.2072-669410.3390/cancers12071784https://hdl.handle.net/20.500.14352/96685Background: 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://doi.org/10.3390/cancers12071784https://www.mdpi.com/journal/cancersopen access616-006.04612.017519.237Basal/squamous-like tumorsBladder cancerImmunohistochemistryMolecular taxonomyNeoadjuvant chemotherapyOncologíaInmunologíaAnálisis Multivariante3207.13 Oncología2412 Inmunología1209.09 Análisis Multivariante