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Eichenauer, Till; Simmendinger, Luca; Fraune, Christoph; Mandelkow, Tim; Blessin, Niclas C.; Kluth, Martina; Hube-Magg, Claudia; Möller, Katharina; Clauditz, Till; Weidemann, Sören; Dahlem, Roland; Fisch, Margit; Riechardt, Silke; Simon, Ronald; Sauter, Guido; Büscheck, Franziska; Rink, Michael

High level of EZH2 expression is linked to high density of CD8-positive T-lymphocytes and an aggressive phenotype in renal cell carcinoma

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  • Media type: E-Article
  • Title: High level of EZH2 expression is linked to high density of CD8-positive T-lymphocytes and an aggressive phenotype in renal cell carcinoma
  • Contributor: Eichenauer, Till; Simmendinger, Luca; Fraune, Christoph; Mandelkow, Tim; Blessin, Niclas C.; Kluth, Martina; Hube-Magg, Claudia; Möller, Katharina; Clauditz, Till; Weidemann, Sören; Dahlem, Roland; Fisch, Margit; Riechardt, Silke; Simon, Ronald; Sauter, Guido; Büscheck, Franziska; Rink, Michael
  • imprint: Springer Science and Business Media LLC, 2021
  • Published in: World Journal of Urology
  • Language: English
  • DOI: 10.1007/s00345-020-03200-4
  • ISSN: 0724-4983; 1433-8726
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>Enhancer of zeste homolog 2 (EZH2), the catalytic part of the Polycomb repressive complex 2 (PRC2), has a prognostic role in renal cell carcinoma (RCC) and was recently shown to modulate the immune response by reducing tumor cell immunogenicity.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>To investigate whether the prognostic role of EZH2 might be driven by a modified immune environment, more than 1800 RCCs were analyzed in a tissue microarray for EZH2 expression and CD8 positive lymphocytes were quantitated by automated digital imaging.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>EZH2 positivity was found in 75.2% of 1603 interpretable tumors. In clear cell RCC, high EZH2 expression was significantly linked to high ISUP, Furmann, and Thoenes grade (<jats:italic>p</jats:italic> &lt; 0.0001 each), advanced stage (<jats:italic>p</jats:italic> &lt; 0.0001), nodal (<jats:italic>p</jats:italic> = 0.0190) and distant metastasis (<jats:italic>p</jats:italic> &lt; 0.0001) as well as shortened overall (<jats:italic>p</jats:italic> &lt; 0.0027) and recurrence free survival (<jats:italic>p</jats:italic> &lt; 0.0001). The density of CD8+ cells varied from 0 to 5048 cells/mm<jats:sup>2</jats:sup> (Median 120 cells/mm<jats:sup>2</jats:sup>). A high CD8+ count was significantly associated with high ISUP, Fuhrmann, and Thoenes grade (<jats:italic>p</jats:italic> &lt; 0.0001 each), advanced tumor stage (<jats:italic>p</jats:italic> = 0.0041), distant metastasis (<jats:italic>p</jats:italic> = 0.0026) as well as reduced overall survival (<jats:italic>p</jats:italic> = 0.0373) and recurrence free survival (<jats:italic>p</jats:italic> = 0.0450). The density of CD8+ cells continuously increased with raising EZH2 levels (<jats:italic>p</jats:italic> &lt; 0.0001).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Our data support a striking prognostic role of both EZH2 expression and the density of CD8+ cells in RCC. The tight relationship of EZH2 expression and CD8+ cell counts in RCC is consistent with models suggesting that EZH2 overexpression can be caused by high lymphocyte content in certain tumor types. Such a mechanism could explain the unique finding of high lymphocyte counts driving poor prognosis in RCC patients.</jats:p> </jats:sec>