Epithelial phenotype as a predictive marker for response to EGFR-TKIs in non-small cell lung cancer patients with wild-type EGFR.
Epithelial-to-mesenchymal transition (EMT) has profound impacts on cancer progression and also on drug resistance, including epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Nowadays, there is still no predictive biomarker identified for the use of EGFR-TKIs in non-small cell lung cancer (NSCLC) patients with wild-type EGFR. To clarify the role of EMT phenotype as a predictive marker for EGFR-TKI, we performed a retrospective study in 202 stage IV or recurrent NSCLC patients receiving gefitinib or erlotinib therapy from June 2008 to September 2012 in our institute. Clinical data and EGFR mutational status were collected, while epithelial, epithelial to mesenchymal, not specified or mesenchymal phenotype were classified according to EMT markers such as E-cadherin, fibronectin, N-cadherin and vimentin by immunohistochemistry. Epithelial phenotype was more frequently found in patients with EGFR mutation (p = 0.044). Epithelial phenotype was associated with a significantly higher objective response rate (23.5 vs. 11.1 vs. 0.0 vs. 2.4%, p = 0.011), longer progression-free survival (4.4 vs. 1.9 vs. 1.7 vs. 1.0 months, p < 0.001) and longer overall survival (11.5 vs. 8.9 vs. 4.5 vs. 4.9 months, p < 0.001) compared to epithelial to mesenchymal, not specified and mesenchymal phenotype in the wild-type EGFR subgroup. In the subgroup with EGFR mutation, the trend remained but without a statistically significant difference. In conclusion, epithelial phenotype was more likely expressed in patients with EGFR mutation and was associated with a better outcome in advanced NSCLC patients with wild-type EGFR, which indicates that the EMT phenotype might be a potential marker to guide EGFR-TKI therapy in this population.
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, People's Republic of China.
Shengxiang
S
Ren
Chunxia
C
Su
Zhaoye
Z
Wang
Jiayu
J
Li
Lihong
L
Fan
Bing
B
Li
Xuefei
X
Li
Cao
C
Zhao
Chunyan
C
Wu
Likun
L
Hou
Yayi
Y
He
Guanghui
G
Gao
Xiaoxia
X
Chen
Jiawei
J
Ren
Aiwu
A
Li
Guotong
G
Xu
Xiao
X
Zhou
Caicun
C
Zhou
Gerald
G
Schmid-Bindert
D000368:Aged; D015703:Antigens, CD; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D004848:Epithelium / Q000473:pathology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014746:Vimentin / Q000378:metabolism
D015703:Antigens, CD; D015415:Biomarkers; C513384:CDH1 protein, human; D015820:Cadherins; D005353:Fibronectins; D047428:Protein Kinase Inhibitors; D014746:Vimentin; C512478:EGFR protein, human; D066246:ErbB Receptors
EGFR tyrosine kinase inhibitor; EMT phenotype; NSCLC; wild-type EGFR