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.
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.
Authors: Nele Van Der Steen; Patrick Pauwels; Ignacio Gil-Bazo; Eduardo Castañon; Luis Raez; Federico Cappuzzo; Christian Rolfo Journal: Cancers (Basel) Date: 2015-03-25 Impact factor: 6.639
Authors: Sherise D Ferguson; Siyuan Zheng; Joanne Xiu; Shouhao Zhou; Mustafa Khasraw; Priscilla K Brastianos; Santosh Kesari; Jethro Hu; Jeremy Rudnick; Michael E Salacz; David Piccioni; Suyun Huang; Michael A Davies; Isabella C Glitza; John V Heymach; Jianjun Zhang; Nuhad K Ibrahim; John F DeGroot; Joseph McCarty; Barbara J O'Brien; Raymond Sawaya; Roeland G W Verhaak; Sandeep K Reddy; Waldemar Priebe; Zoran Gatalica; David Spetzler; Amy B Heimberger Journal: Int J Cancer Date: 2018-10-09 Impact factor: 7.396