Immunohistochemistry-Based Taxonomical Classification of Bladder Cancer Predicts Response to Neoadjuvant Chemotherapy

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-def...

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Detalles Bibliográficos
Autores: Font, Albert|||0000-0003-3908-1111, Domènech, Montserrat|||0000-0003-3973-0986, Benítez, Raquel|||0000-0002-3547-9467, Rava, Marta|||0000-0003-2260-9370, Marqués, Miriam|||0000-0003-1550-3033, Ramirez, Jose Luis, Pineda, Silvia|||0000-0003-4017-1480, Domínguez-Rodríguez, Sara|||0000-0003-3747-9265, Gago Ramos, José Luis, Badal Lafulla, Josep, Carrato, Cristina|||0000-0002-1953-8287, López, Héctor, Quer, Ariadna, Castellano, Daniel|||0000-0002-9106-0687, Malats, Núria|||0000-0003-2538-3784, Real, Francisco X.|||0000-0001-9501-498X
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:252738
Acceso en línea:https://ddd.uab.cat/record/252738
https://dx.doi.org/urn:doi:10.3390/cancers12071784
Access Level:acceso abierto
Palabra clave:Bladder cancer
Neoadjuvant chemotherapy
Molecular taxonomy
Immunohistochemistry
Basal/squamous-like tumors
Descripción
Sumario: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.

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