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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; Ra, Seong; Konety, Badrinath R.; Seiler, Roland; Daneshmand, Siamak; [...]

Molecular Characterization of Neuroendocrine-like Bladder Cancer

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  • Medientyp: E-Artikel
  • Titel: Molecular Characterization of Neuroendocrine-like Bladder Cancer
  • Beteiligte: 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; Ra, Seong; Konety, Badrinath R.; Seiler, Roland; Daneshmand, Siamak; [...]
  • Erschienen: American Association for Cancer Research (AACR), 2019
  • Erschienen in: Clinical Cancer Research, 25 (2019) 13, Seite 3908-3920
  • Sprache: Englisch
  • DOI: 10.1158/1078-0432.ccr-18-3558
  • ISSN: 1078-0432; 1557-3265
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Experimental Design:</jats:title> <jats:p>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; 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 5 validation cohorts (n = 1302). Uni- and multivariable survival analyses were used to characterize clinical outcomes.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>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; P = 0.046) and, after adjusting for clinical and pathologic factors, had a 6.4-fold increased risk of all-cause mortality (P = 0.001). IHC confirmed the neuronal character of these tumors.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>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.</jats:p> </jats:sec>
  • Zugangsstatus: Freier Zugang