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

Author:

de Jong Joep J1ORCID,Narayan Vikram M23,Cronican Andrea A4,Gupta Shilpa56,van Leenders Geert J L H7,Boormans Joost L1,Gibb Ewan A4,Konety Badrinath R1

Affiliation:

1. Department of Urology, Erasmus MC, Cancer Institute Rotterdam,The Netherlands

2. Department of Urology, University of Minnesota, Minneapolis, MN, USA

3. Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX

4. Decipher Biosciences, Vancouver, Canada

5. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, USA

6. Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH

7. Department of Pathology, Erasmus MC, Cancer Institute Rotterdam, The Netherlands

Abstract

Abstract 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.

Funder

Decipher Biosciences

Publisher

Oxford University Press (OUP)

Subject

General Medicine

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