Immunohistochemistry-based taxonomical classification of bladder cancer predicts response to neoadjuvant chemotherapy

Font, Albert; Doménech, Montserrat; Benítez, Raquel; Rava, Marta; Marqués, Miriam; Ramirez, Jose Luis; Pineda, Silvia; Domínguez Rodríguez, Miriam; Gago, José L.; Badal, Josep; Carrato, Cristina; López, Héctor; Quer, Ariadna; Castellano, Daniel; Malats i Riera, Núria; Real, Francisco X.

doi:http://dx.doi.org/10.3390/cancers12071784

Immunohistochemistry-based taxonomical classification of bladder cancer predicts response to neoadjuvant chemotherapy

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

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.