BACKGROUND AND OBJECTIVE: Small molecular inhibitors of the epidermal growth factor receptor (EGFR) have been extensively studied in non-small cell lung cancer (NSCLC) patients. The discovery of molecular biomarkers that identify the subgroups of NSCLC patients benefiting from EGFR tyrosine kinase inhibitor (TKI) has become an important area of investigation. Recent studies have suggested that epithelial-mesenchymal transition (EMT) in tumours decreases the cellular requirements for EGFR signalling pathway, and this may provide a molecular signature to define those NSCLC patients most likely to respond to treatment with targeted EGFR TKI. This research explored the clinicopathological features and EGFR mutations associated with EMT in NSCLC. METHODS: The EMT status in surgically resected specimens from 62 patients with NSCLC was tested by immunohistochemical staining. The frequency of tumour epithelial phenotype was calculated and the strength of the association with clinicopathological features and EGFR genotype was determined by logistic regression. RESULTS: The overall frequency of the epithelial phenotype was 35.48% (22 of 62). Based on univariate analyses, the frequency of the epithelial phenotype (E-cadherin-positive) was greater for EGFR mutants versus wild types (77.78% vs 18.18%; P < 0.0001) and women versus men (54.55% vs 25%; P = 0.02). Multivariate logistic analysis showed that only the EGFR genotype (odds ratio, 0.063; 95% CI: 0.013-0.3; P = 0.0005) was significantly associated with the epithelial phenotype. CONCLUSION: In patients with NSCLC, there is a higher frequency of epithelial markers in patients with EGFR mutation.
BACKGROUND AND OBJECTIVE: Small molecular inhibitors of the epidermal growth factor receptor (EGFR) have been extensively studied in non-small cell lung cancer (NSCLC) patients. The discovery of molecular biomarkers that identify the subgroups of NSCLCpatients benefiting from EGFR tyrosine kinase inhibitor (TKI) has become an important area of investigation. Recent studies have suggested that epithelial-mesenchymal transition (EMT) in tumours decreases the cellular requirements for EGFR signalling pathway, and this may provide a molecular signature to define those NSCLCpatients most likely to respond to treatment with targeted EGFR TKI. This research explored the clinicopathological features and EGFR mutations associated with EMT in NSCLC. METHODS: The EMT status in surgically resected specimens from 62 patients with NSCLC was tested by immunohistochemical staining. The frequency of tumour epithelial phenotype was calculated and the strength of the association with clinicopathological features and EGFR genotype was determined by logistic regression. RESULTS: The overall frequency of the epithelial phenotype was 35.48% (22 of 62). Based on univariate analyses, the frequency of the epithelial phenotype (E-cadherin-positive) was greater for EGFR mutants versus wild types (77.78% vs 18.18%; P < 0.0001) and women versus men (54.55% vs 25%; P = 0.02). Multivariate logistic analysis showed that only the EGFR genotype (odds ratio, 0.063; 95% CI: 0.013-0.3; P = 0.0005) was significantly associated with the epithelial phenotype. CONCLUSION: In patients with NSCLC, there is a higher frequency of epithelial markers in patients with EGFR mutation.
Authors: Mark J Schliekelman; Ayumu Taguchi; Jun Zhu; Xudong Dai; Jaime Rodriguez; Muge Celiktas; Qing Zhang; Alice Chin; Chee-Hong Wong; Hong Wang; Lisa McFerrin; Suhaida A Selamat; Chenchen Yang; Evan M Kroh; Kavita S Garg; Carmen Behrens; Adi F Gazdar; Ite A Laird-Offringa; Muneesh Tewari; Ignacio I Wistuba; Jean P Thiery; Samir M Hanash Journal: Cancer Res Date: 2015-03-05 Impact factor: 12.701
Authors: Tetsunari Hase; Mitsuo Sato; Kenya Yoshida; Luc Girard; Yoshihiro Takeyama; Mihoko Horio; Momen Elshazley; Tomoyo Oguri; Yoshitaka Sekido; David S Shames; Adi F Gazdar; John D Minna; Masashi Kondo; Yoshinori Hasegawa Journal: Cancer Sci Date: 2011-06-02 Impact factor: 6.716
Authors: Ayumu Taguchi; Katerina Politi; Sharon J Pitteri; William W Lockwood; Vitor M Faça; Karen Kelly-Spratt; Chee-Hong Wong; Qing Zhang; Alice Chin; Kwon-Sik Park; Gary Goodman; Adi F Gazdar; Julien Sage; Daniela M Dinulescu; Raju Kucherlapati; Ronald A Depinho; Christopher J Kemp; Harold E Varmus; Samir M Hanash Journal: Cancer Cell Date: 2011-09-13 Impact factor: 31.743
Authors: Andrej Pala; Georg Karpel-Massler; Richard Eric Kast; Christian Rainer Wirtz; Marc-Eric Halatsch Journal: Cancers (Basel) Date: 2012-05-08 Impact factor: 6.639