Gene Expression Profiling of Muscle-Invasive Bladder Cancer With Secondary Variant Histology

Am J Clin Pathol. 2021 Oct 13;156(5):895-905. doi: 10.1093/ajcp/aqab047.


Objectives: To determine the potential impact of the presence of secondary variant histology on the gene expression profiles of muscle-invasive bladder cancer (MIBC) tumors.

Methods: For six tumors, revised samples were collected from urothelial and secondary variant components (cohort A). The commercial cohort (cohort B) consisted of the anonymized gene expression profiles of 173 patients with MIBC. Samples were obtained from the clinical use of the Decipher Bladder test that were available as part of the Decipher GRID prospective registry (NCT02609269). Secondary variant presence in cohort B was abstracted from institutional pathology reports. For the commercial cohort, only the urothelial carcinoma component was profiled.

Results: Molecular subtyping of both urothelial and variant components found micropapillary and nested cases were classified as a luminal subtype. Conversely, the sarcomatoid and small cell cases were classified as basal/squamous or neuroendocrine-like, respectively. For cohort B, 50 (29%) of 173 cases had reported secondary variant histology. Cases with squamous variant had basal profiles, small cell cases expressed neuronal markers, and micropapillary cases were classified as luminal. Sarcomatoid tumors had robust epithelial-mesenchymal transition marker expression.

Conclusions: Our data suggest that in MIBC with secondary variant, the urothelial component can demonstrate an expression profile that closely resembles the variant component.

Keywords: Gene expression analysis; Molecular subtypes; Muscle-invasive bladder cancer; Urothelial carcinoma; Variant histology.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / pathology*
  • Gene Expression Profiling*
  • Humans
  • Male
  • Middle Aged
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*


  • Biomarkers, Tumor