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Multilayer spectrum of intratumoral heterogeneity in basal bladder cancer.
Sirab, Nanor; Drubay, Damien; Maillé, Pascale; Popova, Tatiana; Ngo, Carine; Gentien, David; Moktefi, Anissa; Soyeux-Porte, Pascale; Pelletier, Romain; Reyes, Cécile; Henry, Emilie; Pouessel, Damien; Vordos, Dimitri; Lebret, Thierry; de Reyniès, Aurélien; Paoletti, Xavier; Radvanyi, François; Allory, Yves.
Afiliação
  • Sirab N; Institut Curie, CNRS, UMR144, Molecular Oncology Team, PSL Research University, Paris, France.
  • Drubay D; Gustave Roussy, Service de Biostatistique et d'Epidémiologie, INSERM U1018, CESP, Université Paris-Saclay, Villejuif, France.
  • Maillé P; Department of Pathology, AP-HP, Hôpital Henri Mondor, Créteil, France.
  • Popova T; Institut Curie, INSERM, U830, DNA Repair and Uveal Melanoma (D.R.U.M.) Team, Paris, France.
  • Ngo C; Université Paris-Est, U955 INSERM, Institut Mondor de Recherche Biomédicale, Créteil, France.
  • Gentien D; Institut Curie, Translational Research Department, Genomic Platform, PSL Research University, Paris, France.
  • Moktefi A; Department of Pathology, AP-HP, Hôpital Henri Mondor, Créteil, France.
  • Soyeux-Porte P; Université Paris-Est, U955 INSERM, Institut Mondor de Recherche Biomédicale, Créteil, France.
  • Pelletier R; Department of Pathology, AP-HP, Hôpital Henri Mondor, Créteil, France.
  • Reyes C; Institut Curie, Translational Research Department, Genomic Platform, PSL Research University, Paris, France.
  • Henry E; Institut Curie, Translational Research Department, Genomic Platform, PSL Research University, Paris, France.
  • Pouessel D; Department of Medical Oncology, Institut Universitaire du Cancer Oncopole de Toulouse, Toulouse, France.
  • Vordos D; Department of Urology, AP-HP, Hôpital Henri Mondor, Créteil, France.
  • Lebret T; Department of Urology, Hôpital Foch, Suresnes, France.
  • de Reyniès A; Université de Versailles-Saint-Quentin-en-Yvelines, UFR Santé Simone Veil, Guyancourt, France.
  • Paoletti X; Ligue Nationale Contre Le Cancer, Cartes D'Identité Des Tumeurs Program, Paris, France.
  • Radvanyi F; Université de Versailles-Saint-Quentin-en-Yvelines, UFR Santé Simone Veil, Guyancourt, France.
  • Allory Y; Institut Curie, INSERM, U900, Statistical Methods for Precision Medicine (StaMPM), Saint-Cloud, France.
J Pathol ; 256(1): 108-118, 2022 01.
Article em En | MEDLINE | ID: mdl-34611919
Basal/squamous (Ba/Sq) subtype represents an intrinsic and robust group in the consensus molecular classification of muscle-invasive bladder cancer (MIBC), with poor outcome and controversial chemosensitivity. We aimed to investigate the spectrum of intratumor heterogeneity (ITH) in the Ba/Sq subtype. First, we validated a 29-gene NanoString CodeSet to predict the Ba/Sq subtype for FFPE samples. We identified heterogeneous Ba/Sq tumors in a series of 331 MIBC FFPE samples using dual GATA3/KRT5/6 immunohistochemistry (IHC). Heterogeneous regions with distinct immunostaining patterns were studied separately for gene expression using the 29-gene CodeSet, for mutations by targeted next-generation sequencing, and for copy number alteration (CNA) by microarray hybridization. Among 83 Ba/Sq tumors identified by GATA3/KRT5/6 dual staining, 19 tumors showed heterogeneity at the IHC level. In one third of the 19 cases, regions from the same tumor were classified in different distinct molecular subtypes. The mutational and CNA profiles confirmed the same clonal origin for IHC heterogeneous regions with possible subclonal evolution. Overall, two patterns of intratumoral heterogeneity (ITH) were observed in Ba/Sq tumors: low ITH (regions with distinct immunostaining, but common molecular subtype and shared CNA) or high ITH (regions with distinct immunostaining, molecular subtype, and CNA). These results showed multilayer heterogeneity in Ba/Sq MIBC. In view of personalized medicine, this heterogeneity adds complexity and should be taken into account for sampling procedures used for diagnosis and treatment choice. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Biomarcadores Tumorais / Variações do Número de Cópias de DNA / Mutação Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Biomarcadores Tumorais / Variações do Número de Cópias de DNA / Mutação Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article