Epithelial-mesenchymal transition, proliferation, and angiogenesis in locally advanced cervical cancer treated with chemoradiotherapy

We evaluated the association between epithelial-mesenchymal transition (EMT)-derived markers and expression of proteins associated with cell proliferation and tumor growth, as well as their prognostic roles, in 61 patients (mean age 52 +/- 10years) with locally advanced cervical cancer, all of whom were treated with chemoradiation and intracavitary brachytherapy. We used immunohistochemical analysis to assess the expression of proteins targeted in our investigation. Various statistical analyses were then conducted to assess protein marker associations with survival outcomes. Forty-six percent of the patients were positive for human papilloma virus. Median progression-free survival (PFS) was 6.6months (95% confidence interval [CI]: 4.0-9.1, whereas overall survival (OS) was 30.0months (95% CI: 11-48). Multivariate analysis demonstrated that vascular endothelial growth factor (VEGF) (P=0.002), epidermal growth factor receptor (EGFR) (P=0.001), and TWIST2 (P=0.001) expression levels, as well as a tumor size <6cm (P=0.02), influenced OS. Changes in TWIST2 levels and loss of E-cadherin expression were correlated with VEGF and EGFR levels; furthermore, patients with high TWIST2 expression had shorter OS (P=0.0001), as those with loss of E-cadherin (P=0.02). OS was even shorter when positive EGFR or VEGF expression was related with EMT markers (positive EGFR + negative E-cadherin: median 14months, 95% CI: 3-24; negative EGFR + positive E-cadherin: median 31months, 95% CI: 14-NA; P=0.02.). The presence of EMT markers was associated with proliferative and pro-angiogenic protein expression and influenced the prognosis of locally advanced cervical cancer.