BACKGROUND: The epithelial to mesenchymal transition (EMT) may well play a part in determining the sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). However to date, no study has investigated the association between the EMT status and acquired resistance using cancer specimens. PATIENTS AND METHODS: Immunohistochemical (IHC) staining was used to analyse the protein expression of epithelial and mesenchymal markers in tumour samples from lung adenocarcinoma patients. Mutations in the EGFR and K-ras gene were also examined. RESULTS: All patients showed a positive expression of epithelial markers in sensitive tumours. Tumour in 4 (44.4%) out of 9 patients showed down-regulation of epithelial markers or up-regulation of mesenchymal markers. The change in the EMT status between pre-and post-treatment was shown in 2 cases each with and without the T790M mutation. CONCLUSION: EMT plays a role in approximately half of the cases of resistance to EGFR-TKI, independent of T790M mutation.
BACKGROUND: The epithelial to mesenchymal transition (EMT) may well play a part in determining the sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). However to date, no study has investigated the association between the EMT status and acquired resistance using cancer specimens. PATIENTS AND METHODS: Immunohistochemical (IHC) staining was used to analyse the protein expression of epithelial and mesenchymal markers in tumour samples from lung adenocarcinomapatients. Mutations in the EGFR and K-ras gene were also examined. RESULTS: All patients showed a positive expression of epithelial markers in sensitive tumours. Tumour in 4 (44.4%) out of 9 patients showed down-regulation of epithelial markers or up-regulation of mesenchymal markers. The change in the EMT status between pre-and post-treatment was shown in 2 cases each with and without the T790M mutation. CONCLUSION: EMT plays a role in approximately half of the cases of resistance to EGFR-TKI, independent of T790M mutation.
Authors: Robert M Gemmill; Patrick Nasarre; Joyce Nair-Menon; Federico Cappuzzo; Lorenza Landi; Armida D'Incecco; Hidetaka Uramoto; Takeshi Yoshida; Eric B Haura; Kent Armeson; Harry A Drabkin Journal: Sci Signal Date: 2017-01-17 Impact factor: 8.192
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