IBCN 2018: Signature Immunohistochemical Classifier of Molecular Subtypes in Bladder Cancer

Rotterdam, The Netherlands (UroToday.com) Charles Guo presented their work regarding the identification of signature immunohistochemical markers that would permit simple and cost-effective classification of the disease in routine clinical practice. They analyzed genomic expression profiles of formalin-fixed paraffin embedded bladder cancer samples (n=74) to validate the expression signatures of luminal and basal subtypes and relate them to clinical data.

They also performed immunohistochemistry on the matched tumor samples to identify immunohistochemical markers that permitted the molecular classification of bladder cancer. Genomic expression analysis divided the cohort into two distinct molecular subtypes, luminal (n=57) and basal (n=17). Luminal tumors were characterized by the expression signature similar to the intermediate/superficial layers of normal urothelium, including overexpression of KRT7, KRT8, KRT18, KRT20, and GATA3 genes. 

Additionally, they showed the upregulation of E-Cadherin, HER2/3, Rab-25, Src and PPARγ-target genes. Basal tumors were characterized by the expression signature similar to the basal layer of normal urothelium, including overexpression of KRT 1, KRT5, KRT 6, KRT14, and KRT16. Additionally, basal tumors showed the upregulation of CD49, Cyclin B1, EGFR, and p63- target genes. Basal versus luminal tumors had worse survival. The immunohistochemical expressions of only two markers, luminal (GATA3) and basal (KRT5/6), were sufficient to identify the molecular subtypes of bladder cancer with over 90% accuracy. 

In conclusion, basal and luminal molecular subtypes of bladder cancer have distinct clinical behaviors and sensitivities to chemotherapy, and a simple two-marker immunohistochemical classifier can be used for prognostic and therapeutic stratification. A ‘simple and easy’ clinical application of current molecular subtype systems are needed which provide a cost-effective means to classify these tumors to then implement and disseminate in the clinical setting. 

Presented by: Charles Guo, The University of Texas MD Anderson Cancer Center, Houston, TX 

Written by: Stephen B. Williams, M.D., Associate Professor, Division of Urology, The University of Texas Medical Branch, Galveston, TX. and Ashish M. Kamat, M.D. Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 16th Annual Meeting of the International Bladder Cancer Network (IBCN) October 11-13, 2018 - the Inntel Hotels Rotterdam Centre, Rotterdam, The Netherlands
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