• Media type: E-Article
  • Title: Amplification and overexpression of CMET is a common event in brain metastases of non‐small cell lung cancer
  • Contributor: Preusser, Matthias; Streubel, Berthold; Berghoff, Anna S; Hainfellner, Johannes A; von Deimling, Andreas; Widhalm, Georg; Dieckmann, Karin; Wöhrer, Adelheid; Hackl, Monika; Zielinski, Christoph; Birner, Peter
  • Published: Wiley, 2014
  • Published in: Histopathology
  • Extent: 684-692
  • Language: English
  • DOI: 10.1111/his.12475
  • ISSN: 0309-0167; 1365-2559
  • Keywords: General Medicine ; Histology ; Pathology and Forensic Medicine
  • Abstract: <jats:sec><jats:title>Background</jats:title><jats:p><jats:styled-content style="fixed-case">CMET</jats:styled-content> represents an emerging therapy target for monoclonal antibodies and tyrosine kinase inhibitors in non‐small cell lung cancer (<jats:styled-content style="fixed-case">NSCLC</jats:styled-content>).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We investigated <jats:styled-content style="fixed-case">C<jats:italic>MET</jats:italic></jats:styled-content> gene amplification status by fluorescence <jats:italic>in‐situ</jats:italic> hybridization (<jats:styled-content style="fixed-case">FISH</jats:styled-content>) and <jats:styled-content style="fixed-case">CMET</jats:styled-content> protein expression by immunohistochemistry in a large series of 209 <jats:styled-content style="fixed-case">NSCLC</jats:styled-content> brain metastases (<jats:styled-content style="fixed-case">BM</jats:styled-content>; 165 adenocarcinoma, 20 squamous cell carcinoma, 11 adenosquamous carcinomas, 11 large cell carcinomas and two large cell neuroendocrine carcinomas) and correlated our results to clinic‐pathological parameters and molecular data from previous studies.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We found <jats:italic><jats:styled-content style="fixed-case">CMET</jats:styled-content></jats:italic> gene amplification in 36/167 (21.6%) and <jats:styled-content style="fixed-case">CMET</jats:styled-content> protein expression in 87/196 (44.4%) of evaluable <jats:styled-content style="fixed-case">BM</jats:styled-content>. There was a strong correlation between the presence of <jats:styled-content style="fixed-case">C<jats:italic>MET</jats:italic></jats:styled-content> gene amplification and <jats:styled-content style="fixed-case">CMET</jats:styled-content> protein expression (<jats:italic>P</jats:italic> &lt; 0.001, chi‐square test). Furthermore, presence of <jats:styled-content style="fixed-case">C<jats:italic>MET</jats:italic></jats:styled-content> amplification correlated positively with presence of <jats:italic><jats:styled-content style="fixed-case">ALK</jats:styled-content></jats:italic> amplifications (<jats:italic>P</jats:italic> = 0.039, chi‐square test) and high <jats:styled-content style="fixed-case">HIF</jats:styled-content>1 alpha index (<jats:italic>P</jats:italic> = 0.013, Mann–Whitney <jats:italic>U</jats:italic>‐test). Neither <jats:styled-content style="fixed-case">CMET</jats:styled-content> expression nor <jats:italic><jats:styled-content style="fixed-case">CMET</jats:styled-content></jats:italic> gene amplification status correlated with patient outcome parameters or known prognostic factors.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p><jats:styled-content style="fixed-case">CMET</jats:styled-content> overexpression and <jats:italic><jats:styled-content style="fixed-case">CMET</jats:styled-content></jats:italic> amplification are commonly found in <jats:styled-content style="fixed-case">NSCLC BM</jats:styled-content> and may represent a promising therapeutic target.</jats:p></jats:sec>
  • Description: <jats:sec><jats:title>Background</jats:title><jats:p><jats:styled-content style="fixed-case">CMET</jats:styled-content> represents an emerging therapy target for monoclonal antibodies and tyrosine kinase inhibitors in non‐small cell lung cancer (<jats:styled-content style="fixed-case">NSCLC</jats:styled-content>).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We investigated <jats:styled-content style="fixed-case">C<jats:italic>MET</jats:italic></jats:styled-content> gene amplification status by fluorescence <jats:italic>in‐situ</jats:italic> hybridization (<jats:styled-content style="fixed-case">FISH</jats:styled-content>) and <jats:styled-content style="fixed-case">CMET</jats:styled-content> protein expression by immunohistochemistry in a large series of 209 <jats:styled-content style="fixed-case">NSCLC</jats:styled-content> brain metastases (<jats:styled-content style="fixed-case">BM</jats:styled-content>; 165 adenocarcinoma, 20 squamous cell carcinoma, 11 adenosquamous carcinomas, 11 large cell carcinomas and two large cell neuroendocrine carcinomas) and correlated our results to clinic‐pathological parameters and molecular data from previous studies.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We found <jats:italic><jats:styled-content style="fixed-case">CMET</jats:styled-content></jats:italic> gene amplification in 36/167 (21.6%) and <jats:styled-content style="fixed-case">CMET</jats:styled-content> protein expression in 87/196 (44.4%) of evaluable <jats:styled-content style="fixed-case">BM</jats:styled-content>. There was a strong correlation between the presence of <jats:styled-content style="fixed-case">C<jats:italic>MET</jats:italic></jats:styled-content> gene amplification and <jats:styled-content style="fixed-case">CMET</jats:styled-content> protein expression (<jats:italic>P</jats:italic> &lt; 0.001, chi‐square test). Furthermore, presence of <jats:styled-content style="fixed-case">C<jats:italic>MET</jats:italic></jats:styled-content> amplification correlated positively with presence of <jats:italic><jats:styled-content style="fixed-case">ALK</jats:styled-content></jats:italic> amplifications (<jats:italic>P</jats:italic> = 0.039, chi‐square test) and high <jats:styled-content style="fixed-case">HIF</jats:styled-content>1 alpha index (<jats:italic>P</jats:italic> = 0.013, Mann–Whitney <jats:italic>U</jats:italic>‐test). Neither <jats:styled-content style="fixed-case">CMET</jats:styled-content> expression nor <jats:italic><jats:styled-content style="fixed-case">CMET</jats:styled-content></jats:italic> gene amplification status correlated with patient outcome parameters or known prognostic factors.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p><jats:styled-content style="fixed-case">CMET</jats:styled-content> overexpression and <jats:italic><jats:styled-content style="fixed-case">CMET</jats:styled-content></jats:italic> amplification are commonly found in <jats:styled-content style="fixed-case">NSCLC BM</jats:styled-content> and may represent a promising therapeutic target.</jats:p></jats:sec>
  • Footnote: