Molecular Characterization of Neuroendocrine-like Bladder Cancer.

Batista da Costa, José; Gibb, Ewan A; Bivalacqua, Trinity J; Liu, Yang; Oo, Htoo Zarni; Miyamoto, David T; Alshalalfa, Mohammed; Davicioni, Elai; Wright, Jonathan; Dall'Era, Marc A; Douglas, James; Boormans, Joost L; Van der Heijden, Michiel S; Wu, Chin-Lee; van Rhijn, Bas W G; Gupta, Shilpa; Grivas, Petros; Mouw, Kent W; Murugan, Paari; Fazli, Ladan; ... (2019). Molecular Characterization of Neuroendocrine-like Bladder Cancer. Clinical cancer research, 25(13), pp. 3908-3920. American Association for Cancer Research 10.1158/1078-0432.CCR-18-3558

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Neuroendocrine (NE) bladder carcinoma is a rare and aggressive variant. Molecular subtyping studies have found that 5% to 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. Transcriptome-wide expression profiles were generated for MIBC collected from 7 institutions and clinical-use of Decipher Bladder. Using unsupervised clustering, we generated a clustering solution on a prospective training cohort (PTC; = 175), developed single-sample classifiers to predict NE tumors, and evaluated the resultant models on a testing radical cystectomy (RC) cohort ( = 225). A random forest model was finalized and applied to 5 validation cohorts ( = 1302). Uni- and multivariable survival analyses were used to characterize clinical outcomes. In the training cohort (PTC), hierarchical clustering using an 84-gene panel showed a cluster of 8 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 6.6% of cases in validation cohorts. Patients with NE-like tumors had significantly worse 1-year progression-free survival (65% NE-like vs. 82% overall; = 0.046) and, after adjusting for clinical and pathologic factors, had a 6.4-fold increased risk of all-cause mortality ( = 0.001). IHC confirmed the neuronal character of these tumors. A single-patient classifier was developed that identifies patients with histologic urothelial cancer harboring a NE transcriptomic profile. These tumors represent a high-risk subgroup of MIBC, which may require different treatment.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Seiler, Roland

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1078-0432

Publisher:

American Association for Cancer Research

Language:

English

Submitter:

Jeannine Wiemann

Date Deposited:

17 Jul 2019 08:59

Last Modified:

24 Oct 2019 12:19

Publisher DOI:

10.1158/1078-0432.CCR-18-3558

PubMed ID:

30952638

BORIS DOI:

10.7892/boris.130768

URI:

https://boris.unibe.ch/id/eprint/130768

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