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Open AccessArticle

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

1
Medical Oncology Department, Institut Català d'Oncologia, Badalona Applied Research group in Oncology (B-ARGO Group), University Hospital Germans Trias I Pujol, 08916 Badalona, Spain
2
Medical Oncology Department, Fundació Althaia, 08243 Manresa, Spain
3
Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain
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Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain
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Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain
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IGTP-Molecular Biology Laboratory, Institut Germans Trias i Pujol, 08916 Badalona, Spain
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Urology Department, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain
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Pathology Department, Fundació Althaia, 08243 Manresa, Spain
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Pathology Department, Hospital Germans Trias i Pujol, 08916 Badalona, Spain
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Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
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Urology Department, Fundació Althaia, 08243 Manresa, Spain
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Medical Oncology Department, Hospital 12 de Octubre, 28029 Madrid, Spain
13
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08193 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
These authors contribute equally to this study.
These authors contribute equally to this study.
Cancers 2020, 12(7), 1784; https://doi.org/10.3390/cancers12071784
Received: 5 June 2020 / Revised: 25 June 2020 / Accepted: 25 June 2020 / Published: 3 July 2020
(This article belongs to the Section Cancer Biomarkers)
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. View Full-Text
Keywords: bladder cancer; neoadjuvant chemotherapy; molecular taxonomy; immunohistochemistry; basal/squamous-like tumors bladder cancer; neoadjuvant chemotherapy; molecular taxonomy; immunohistochemistry; basal/squamous-like tumors
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MDPI and ACS Style

Font, A.; Domènech, M.; Benítez, R.; Rava, M.; Marqués, M.; Ramírez, J.L.; Pineda, S.; Domínguez-Rodríguez, S.; Gago, J.L.; Badal, J.; Carrato, C.; López, H.; Quer, A.; Castellano, D.; Malats, N.; Real, F.X. Immunohistochemistry-Based Taxonomical Classification of Bladder Cancer Predicts Response to Neoadjuvant Chemotherapy. Cancers 2020, 12, 1784. https://doi.org/10.3390/cancers12071784

AMA Style

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. 2020; 12(7):1784. https://doi.org/10.3390/cancers12071784

Chicago/Turabian Style

Font, Albert; Domènech, Montserrat; Benítez, Raquel; Rava, Marta; Marqués, Miriam; Ramírez, José L.; Pineda, Silvia; Domínguez-Rodríguez, Sara; Gago, José L.; Badal, Josep; Carrato, Cristina; López, Héctor; Quer, Ariadna; Castellano, Daniel; Malats, Núria; Real, Francisco X. 2020. "Immunohistochemistry-Based Taxonomical Classification of Bladder Cancer Predicts Response to Neoadjuvant Chemotherapy" Cancers 12, no. 7: 1784. https://doi.org/10.3390/cancers12071784

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