The Basal to Luminal Transition Classifier for Urothelial Cancer Subtypes - Expert Commentary

The luminal-basal continuum of intrinsic messenger RNA (mRNA) expression-based subtypes is an important framework for understanding the biology of urothelial cancer. Differentiating between the two main molecular subtypes of bladder cancer (basal and luminal) is critical for designing trials based on molecular subtypes. 

A recent study published by Guo et al. in Scientific Reports described the development of a quantitative classifier termed the basal to luminal transition (BLT) score. The investigators analyzed mRNA expression profiles in bladder cancer samples obtained from The Cancer Genome Atlas (TCGA) and MD Anderson Cancer Center (MDACC). The BLT score using classified bladder cancer subtypes with 80–94% sensitivity and 83–93% specificity. 

The investigators validated a simple immunohistochemical classifier using immunohistochemical analysis of luminal (GATA3) and basal (KRT5/6) markers. The study found that the accuracy of molecular subtype prediction based on GATA3 and KRT5/6 immunohistochemical analysis was 89.1%. Because these markers are routinely examined during the initial pathology workup of bladder cancers, the authors argue that semiquantitative visual assessment of these markers in routine pathological preparations is a practical tool for identifying bladder cancer subtypes. 

These findings have important implications for prospective trials for personalized therapy based on mRNA expression subtypes. 

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

  1. Guo CC, Bondaruk J, Yao H, Wang Z, Zhang L, Lee S, Lee JG, Cogdell D, Zhang M, Yang G, Dadhania V, Choi W, Wei P, Gao J, Theodorescu D, Logothetis C, Dinney C, Kimmel M, Weinstein JN, McConkey DJ, Czerniak B. “Assessment of Luminal and Basal Phenotypes in Bladder Cancer.” Sci Rep. 2020 Jun 16;10(1):9743. doi: 10.1038/s41598-020-66747-7. PMID: 32546765
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