Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/10994
Immunohistochemistry-Based Taxonomical Classification of Bladder Cancer Predicts Response to Neoadjuvant Chemotherapy.
Font, Albert | Domènech, Montserrat | Benítez, Raquel | Rava, Marta CNIO | Marqués, Miriam | Ramírez, Jose L | Pineda, Silvia | Domínguez-Rodríguez, Sara | Gago, José L | Badal, Josep | Carrato, Cristina | López, Héctor | Quer, Ariadna | Castellano, Daniel | Malats, Nuria CNIO | Real Arribas, Francisco CNIO
Cancers (Basel). 2020;12(7):1784
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. To investigate whether immunohistochemical (IHC) subtyping predicts NAC response. 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. progression-free survival and disease-specific survival; univariable and multivariate Cox regression models were applied. 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. 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.
BLADDER-CANCER | neoadjuvant chemotherapy | molecular taxonomy | immunohistochemistry | squamous-like tumors | basal