Vimentin expression status is a potential biomarker for brain metastasis development in EGFR-mutant NSCLC patients

Abstract

Background: Despite advances in systemic therapy and improvements in survival for advanced epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), brain metastasis (BM) remains a poor outcome. Previous studies on risk factors for BM occurrence included unselected patients and biomarker prediction of BM in these populations were not well studied. We aimed to identify the role of epithelial mesenchymal transition (EMT) marker and clinical factors predicting BM in EGFR-mutant NSCLC patients. Methods: Advanced EGFR-mutant NSCLC patients in the King Chulalongkorn Memorial Hospital from January 2013 to December 2017 were included. Vimentin expression was assessed by immunohistochemistry. The correlation between vimentin expression and factors associated with BM occurrence was analyzed by univariate and multivariate analyses. Results: 304 patients were enrolled. Of these, 149 patients (49%) developed BM. In multivariate analysis, the occurrence of BM was associated with age <60 years, metastatic disease at diagnosis, and 3 or more metastatic sites. Moreover, positive vimentin expression was also found more common in patients with BM than those without BM (52.4% vs. 27.6%, respectively) and predicted overall BM development in EGFR-mutant patients (OR 2.53, 95% CI, 1.11-5.77; P=0.027). Overall survival (OS) was shorter in vimentinpositive group than in vimentinnegative group. Median OS was 20.0 months (95% CI, 14.51-25.51) and 30.9 months (95% CI, 20.99-40.84), respectively (HR, 1.57; P=0.04). Conclusions: Younger patients with EGFR-mutant NSCLC who had high disease burden were more likely to develop BM. Vimentin served as a biomarker for predicting BM and poor prognostic factor in EGFR-mutant patients. EMT pathway may be considered as a therapeutic target in these high-risk populations.