Molecular classification of muscle-invasive bladder cancer based on a simplified immunohistochemical panel using GATA3, CK5/6 and p16

Authors

  • Robert Terlević Department of Pathology and Cytology, Pula General Hospital, Pula, Croatia https://orcid.org/0000-0002-8060-8678
  • Monika Ulamec Clinical Department of Pathology and Cytology “Ljudevit Jurak“, Clinical Hospital Center Sestre milosrdnice, Zagreb, Croatia; School of Medicine, University of Zagreb, Zagreb, Croatia https://orcid.org/0000-0002-4843-8154
  • Goran Štimac Clinical Department of Urology, Clinical Hospital Center Sestre milosrdnice, Zagreb, Croatia https://orcid.org/0000-0002-2894-8069
  • Jure Murgić School of Medicine, University of Zagreb, Zagreb, Croatia; Clinical Department of Oncology, Clinical Hospital Center Sestre milosrdnice, Zagreb, Croatia
  • Božo Krušlin Clinical Department of Pathology and Cytology “Ljudevit Jurak“, Clinical Hospital Center Sestre milosrdnice, Zagreb, Croatia; School of Medicine, University of Zagreb, Zagreb, Croatia https://orcid.org/0000-0002-0480-1687

DOI:

https://doi.org/10.17305/bb.2023.9242

Keywords:

Urothelial carcinoma, bladder cancer, immunohistochemistry (IHC), molecular subtype, survival analysis

Abstract

The choice of therapy for muscle-invasive bladder cancer (MIBC) could be influenced by the tumor’s molecular subtype. Currently, well-defined consensus subtypes are based on tumor microarray mRNA data. Clearly defined and easy-to-use surrogate molecular subtypes, based on immunohistochemistry (IHC) performed on whole slides, are needed to make subtyping cost-effective and useful in routine work and future research. To aid in the development of a simple immunohistochemical classifier, a retrospective single-center series of 92 cases of localized bladder cancer was identified. Routine IHC for GATA3, cytokeratins 5 and 6 (CK5/6), and p16 was performed on whole tissue blocks containing muscle-invasive disease. Electronic medical records were retrieved and searched for clinical variables, treatment, and survival data. The mean age was 69.6 years, and 73% were males. Conservative treatment was used in 55% of cases, while cystectomy with chemotherapy was used in 45%. GATA3 and CK5/6 expression divided cases into broad luminal and basal subtypes, respectively, while p16 expression was used to subclassify luminal cases into luminal papillary and luminal unstable types according to the consensus molecular classification. When subtyped in this way, GATA3 and CK5/6 negative cases showed worse overall survival. Molecular subtyping of MIBC on whole slides containing muscle-invasive tumor using only three commonly used, consensus-based antibodies, is a feasible and cost-effective method for detecting subtypes of invasive bladder cancer. Future work combining morphological analysis and IHC is needed to fully translate the consensus molecular classification into a comprehensive, cost-effective subtyping strategy.

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Molecular classification of muscle-invasive bladder cancer based on a simplified immunohistochemical panel using GATA3, CK5/6 and p16

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Published

03-11-2023

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Section

Pathology

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How to Cite

1.
Molecular classification of muscle-invasive bladder cancer based on a simplified immunohistochemical panel using GATA3, CK5/6 and p16. Biomol Biomed [Internet]. 2023 Nov. 3 [cited 2024 Jun. 20];23(6):968–975. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/9242