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Comparison of clinicopathological characteristics, gene expression profiles, mutational analysis, and clinical outcomes of pure and mixed small-cell carcinoma of the bladder.
Parimi, Vamsi; Choi, Woonyoung; Feng, Mingxiao; Fong, Megan; Hoffman-Censits, Jean; Kates, Max; Lombardo, Kara A; Comperat, Eva; McConkey, David J; Hahn, Noah M; Esteves, Rodrigo Salgado; Matoso, Andres.
Afiliação
  • Parimi V; Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Choi W; Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Feng M; Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Fong M; Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Hoffman-Censits J; Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Kates M; Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Lombardo KA; Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Comperat E; Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • McConkey DJ; Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
  • Hahn NM; Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Esteves RS; Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Matoso A; Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
Histopathology ; 82(7): 991-1002, 2023 Jun.
Article em En | MEDLINE | ID: mdl-36754853
ABSTRACT

AIMS:

Small cell bladder carcinoma (SCBC) is a rare, divergent form of urothelial carcinoma (UC). We aimed to determine whether pure (n = 16) and mixed (SCBC and UC; n = 30) tumours differed in pathology, gene expression characteristics, genetic alterations, and clinical outcomes. METHODS AND

RESULTS:

Forty (87%) patients received first-line chemotherapy. Twenty-nine patients had no metastatic disease at diagnosis and underwent radical cystectomy. There were no differences in age, sex, race distribution, tumour size, stage at presentation, therapy response with pathological downstaging to ≤ypT1N0, or overall or progression-free survival (PFS) between pure and mixed tumours. There was a longer PFS among downstaged chemotherapy-responding tumours ≤ypT2N0M0 than among unresponsive tumours ≥ypT2 ≥ yN1M1 (P = 0.001). Patients who achieved pathological downstaging with neoadjuvant chemotherapy (n = 10) were stage cT2N0M0 at the time of diagnosis and were alive at the last follow-up (median 37 months), while 46% of patients who failed to achieve pathological downstaging were alive at the last follow-up (median 38 months; P = 0.008). RNA sequencing showed that the UC of mixed SCBC had similar neural expression signatures to pure SCBC. DNA sequencing revealed alterations in TERT (83%), P53 (56%), ARID1A (28%), RB1 (22%), and BRCA2 (11%). Immunohistochemistry for RB1 showed loss of expression in 18/19 (95%) patients, suggesting frequent pathway downregulation despite a low prevalence of RB1 mutation.

CONCLUSION:

Patients with pure and mixed SCBC have similar outcomes and these outcomes are determined by the pathological stage at RC and are best among patients who have pathological downstaging after NAC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Carcinoma de Células de Transição / Carcinoma de Células Pequenas Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Histopathology Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Carcinoma de Células de Transição / Carcinoma de Células Pequenas Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Histopathology Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
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