Amplification and overexpression of CMET is a common event in brain metastases of non-small cell lung cancer
Matthias Preusser
Department of Internal Medicine 1, Medical University of Vienna, Vienna, Austria
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorBerthold Streubel
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAnna S Berghoff
Department of Internal Medicine 1, Medical University of Vienna, Vienna, Austria
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorJohannes A Hainfellner
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Institute of Neurology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAndreas von Deimling
Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
Clinical Cooperation Unit Neuropathology, DKFZ, Heidelberg, Germany
Search for more papers by this authorGeorg Widhalm
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Department of Neurosurgery, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorKarin Dieckmann
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Department of Radiotherapy, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAdelheid Wöhrer
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Institute of Neurology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorMonika Hackl
Austrian National Cancer Registry, Statistics Austria, Vienna, Austria
Search for more papers by this authorChristoph Zielinski
Department of Internal Medicine 1, Medical University of Vienna, Vienna, Austria
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorCorresponding Author
Peter Birner
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
Clinical Cooperation Unit Neuropathology, DKFZ, Heidelberg, Germany
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
Address for correspondence: P Birner, Department of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. e-mail: [email protected]Search for more papers by this authorMatthias Preusser
Department of Internal Medicine 1, Medical University of Vienna, Vienna, Austria
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorBerthold Streubel
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAnna S Berghoff
Department of Internal Medicine 1, Medical University of Vienna, Vienna, Austria
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorJohannes A Hainfellner
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Institute of Neurology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAndreas von Deimling
Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
Clinical Cooperation Unit Neuropathology, DKFZ, Heidelberg, Germany
Search for more papers by this authorGeorg Widhalm
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Department of Neurosurgery, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorKarin Dieckmann
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Department of Radiotherapy, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAdelheid Wöhrer
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Institute of Neurology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorMonika Hackl
Austrian National Cancer Registry, Statistics Austria, Vienna, Austria
Search for more papers by this authorChristoph Zielinski
Department of Internal Medicine 1, Medical University of Vienna, Vienna, Austria
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorCorresponding Author
Peter Birner
Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, Vienna, Austria
Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
Clinical Cooperation Unit Neuropathology, DKFZ, Heidelberg, Germany
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
Address for correspondence: P Birner, Department of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. e-mail: [email protected]Search for more papers by this authorAbstract
Background
CMET represents an emerging therapy target for monoclonal antibodies and tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC).
Methods
We investigated CMET gene amplification status by fluorescence in-situ hybridization (FISH) and CMET protein expression by immunohistochemistry in a large series of 209 NSCLC brain metastases (BM; 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.
Results
We found CMET gene amplification in 36/167 (21.6%) and CMET protein expression in 87/196 (44.4%) of evaluable BM. There was a strong correlation between the presence of CMET gene amplification and CMET protein expression (P < 0.001, chi-square test). Furthermore, presence of CMET amplification correlated positively with presence of ALK amplifications (P = 0.039, chi-square test) and high HIF1 alpha index (P = 0.013, Mann–Whitney U-test). Neither CMET expression nor CMET gene amplification status correlated with patient outcome parameters or known prognostic factors.
Conclusions
CMET overexpression and CMET amplification are commonly found in NSCLC BM and may represent a promising therapeutic target.
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