Molecular Characterization of Neuroendocrine-like Bladder Cancer

José Batista Da Costa, Ewan A. Gibb, Trinity J. Bivalacqua, Yang Liu, Htoo Zarni Oo, David T. Miyamoto, Mohammed Alshalalfa, Elai Davicioni, Jonathan Wright, Marc A. Dall’era, James Douglas, Joost L. Boormans, Michiel S. Van Der Heijden, Chin-lee Wu, Bas W.g. Van Rhijn, Shilpa Gupta, Petros Grivas, Kent W. Mouw, Paari Murugan, Ladan FazliSeong Ra, Badrinath R. Konety, Roland Seiler, Siamak Daneshmand, Omar Y. Mian, Jason A. Efstathiou, Yair Lotan, Peter C. Black

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Purpose: Neuroendocrine (NE) bladder carcinoma is a rare and aggressive variant. Molecular subtyping studies have found that 5-15% of muscle-invasive bladder cancer (MIBC) have transcriptomic patterns consistent with NE bladder cancer in the absence of NE histology. The clinical implications of this NE-like subtype have not been explored in depth. Experimental design: Transcriptome-wide expression profiles were generated for MIBC collected from seven institutions and clinical-use of Decipher Bladder. Using unsupervised clustering, we generated a clustering solution on a prospective training cohort (PTC; n=175), developed single-sample classifiers to predict NE tumors, and evaluated the resultant models on a testing radical cystectomy (RC) cohort (n=225). A random forest model was finalized and applied to five validation cohorts (n=1302). Uni- and multivariable survival analyses were used to characterize clinical outcomes. Results: In the training cohort (PTC), hierarchical clustering using an 84 gene panel showed a cluster of eight patients (4.6%) with highly heterogeneous expression of NE markers in the absence of basal or luminal marker expression. NE-like tumors were identified in 1% to 7.1% of cases in validation cohorts. Patients with NE-like tumors had significantly worse 1-year progression free survival (65% NE-like vs 82% overall; p=0.046) and, after adjusting for clinical and pathological factors, had a 6.4-fold increased risk of all-cause mortality (p=0.001). IHC confirmed the neuronal character of these tumors. Conclusion: A single patient classifier was developed that identifies patients with histological urothelial cancer harboring a NE transcriptomic profile. These tumors represent a high-risk subgroup of MIBC which may require different treatment.
Original languageEnglish (US)
JournalClinical Cancer Research
DOIs
StatePublished - 2019

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Molecular Characterization of Neuroendocrine-like Bladder Cancer'. Together they form a unique fingerprint.

Cite this