Clinicopathological features and epidermal growth factor receptor mutations associated with epithelial-mesenchymal transition in non-small cell lung cancer.
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.


CONCLUSIONS
In patients with NSCLC, there is a higher frequency of epithelial markers in patients with EGFR mutation.
Deng
Qin-Fang
QF
Department of Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
Zhou
Cai-Cun
CC
Su
Chun-Xia
CX
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014746:Vimentin / Q000378:metabolism
D015820:Cadherins; D004791:Enzyme Inhibitors; D014746:Vimentin; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases