The Role of TOP2A Protein Expression and Aneuploidy in NSCLC

Purpose DNA topoisomerase II alpha (TOP2A) is a cell-cycle dependent protein associated with cell proliferation and division. Abnormal regulation of TOP2A and aneuploidy induces tumorigenesis and poor prognosis. Data related to TOP2A protein in non-small cell lung cancer (NSCLC) is limited to few studies on gene status. The present study aimed to investigate the consistency between aneuploidy and expression of TOP2A gene and protein, respectively, and the role of aneuploidy in the prognosis of NSCLC patients. Methods Clinical data and lung cancer tissues were collected from 244 patients with NSCLC. TOP2A protein and gene expression were detected using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. Nonparametric Spearman’s rank sum test was used to analyze clinicopathological data. Kaplan–Meier and multivariate Cox regression methods were used for survival analysis. Results Enhanced expression and amplification rate of TOP2A protein and gene were 29.9% (73/244) and 0.4% (1/244), respectively. The aneuploidy rate was 31.6% (77/244). In NSCLC, patients with enhanced expression of TOP2A protein and aneuploidy correlated with clinical stages (p < 0.001) Enhanced expression of TOP2A protein was consistent with aneuploidy as detected by Kappa test (K = 0.307) and this correlation was confirmed by chi-square test (p < 0.001). The overall survival of patients with aneuploidy was shorter than diploidy (p < 0.001). Clinically advanced patients with aneuploidy together with TOP2A overexpression had poor prognosis (p < 0.001). Conclusion Aneuploidy and overexpression of TOP2A is a predictor of poor prognosis in patients with advanced NSCLC.