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Histopathologic, Molecular, and Clinical Profiling of Lymphoepithelioma-like Carcinoma of the Bladder.
Koll, Florestan Johannes; Weers, Lillian; Weigert, Andreas; Banek, Severine; Köllermann, Jens; Kluth, Luis; Wenzel, Mike; Garcia, Cristina Cano; Szarvas, Tibor; Wessolly, Michael; Ingenwerth, Marc; Jeroch, Jan; Döring, Claudia; Chun, Felix K-H; Wild, Peter J; Reis, Henning.
Afiliação
  • Koll FJ; Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany. Electronic address: Koll@med.uni-frankfurt.de.
  • Weers L; Dr Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • Weigert A; Institute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany.
  • Banek S; Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • Köllermann J; Dr Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • Kluth L; Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • Wenzel M; Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • Garcia CC; Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • Szarvas T; Department of Urology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Department of Urology, Semmelweis University Budapest, Budapest, Hungary.
  • Wessolly M; Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Ingenwerth M; Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Jeroch J; Dr Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • Döring C; Dr Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • Chun FK; Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • Wild PJ; Dr Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • Reis H; Dr Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany. Electronic address: henning.reis@ukffm.de.
Mod Pathol ; 37(11): 100588, 2024 Aug 02.
Article em En | MEDLINE | ID: mdl-39097190
ABSTRACT
Lymphoepithelioma-like carcinoma of the bladder (LELC-B) is a rare histologic subtype characterized by strong immune cell (IC) infiltrates. A better prognosis and favorable response rates to immune checkpoint inhibitors have been described. We aimed to characterize the molecular profiles and IC infiltration of LELC-B for a better understanding of its therapeutic implications. We identified 11 muscle-invasive bladder cancer cases with pure and mixed LELC-B. Programmed cell death ligand-1 (PD-L1) expression and mismatch repair proteins were evaluated using immunohistochemistry. We calculated the tumor mutational burden and characterized mutational profiles using whole-exome DNA sequencing data. Transcriptomic signatures were detected using the NanoString nCounter PanCancer IO360 Panel. Multiplex immunofluorescence of tumor microenvironment (PD-L1, PanCK, α-SMA, vimentin, CD45, and Ki67) and T cells (CD4, CD3, PD-1, CD163, CD8, and FoxP3) was used to quantify cell populations. All LELC-B cases were highly positive for PD-L1 (median tumor proportion score/tumor cell, 70%; range, 20%-100%; median combined positive score, 100; range, 50-100) and mismatch repair proficient and negative for Epstein-Barr virus infection. IC infiltrates were characterized by a high CD8+ T-cell count and high PD-1/PD-L1 expression on immune and tumor cells. LELC-B showed upregulation of signaling pathways involved in IC response. Most common mutations were found in chromatin remodeling genes causing epigenetic dysregulation. All LELC-B cases showed high tumor mutational burden with a median of 39 mutations/Mb (IQR, 29-66 mutations/Mb). In conclusion, LELC-B is a highly immunogenic tumor, showing strong upregulation of PD-1/PD-L1 and making immune checkpoint inhibitors a promising treatment option.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article