Association of low expression of E-cadherin and β-catenin with the progression of early stage human squamous cervical cancer.

Abstract

The precise involvement and mechanisms of human papilloma virus type 16 (HPV16) in epithelial-mesenchymal transition (EMT) of cervical intraepithelial neoplasia (CIN) and squamous cervical cancer (SCC) remain unknown. The present study aimed to examine the expression of EMT indicators and their association with HPV16 in CIN and early stage SCC, and their prognostic value in early stage SCC. The expression levels of E-cadherin, N-cadherin, β-catenin, vimentin, and fibronectin were determined by immunohistochemistry in 40 patients with normal uterine cervix, 22 patients with CIN1, 60 patients with CIN2-3, and 86 patients with SCC, stage Ia-IIa, according to the International Federation of Gynecology and Obstetrics. The expression of the epithelial indicators E-cadherin and β-catenin gradually declined, and the mesenchymal indicators N-cadherin, vimentin, and fibronectin increased with progression of the cervical lesions (P<0.05). Patients with SCC with lymph node metastasis, parametrial invasion, negative E-cadherin, and negative β-catenin expression had shorter overall survival (P=0.001, P=0.015, P=0.014, and P=0.043, respectively) and disease-free survival (P=0.002, P=0.021, P=0.025, and P=0.045, respectively) time. Multivariate survival analysis indicated that lymph node metastasis [Hazard ratio (HR)=3.544; P=0.010], parametrial invasion (HR=2.014; P=0.007) and E-cadherin expression (HR=0.163; P<0.001) were independently associated with overall survival, but also with disease-free survival (HR=3.612, P=0.009; HR=1.935, P=0.011; HR=0.168, P<0.001, respectively). In patients with CINs, HPV16 infection was negatively correlated with the expression of E-cadherin, and positively correlated with the expression of N-cadherin, vimentin, and fibronectin. EMT occurs during the progression of CINs to early stage SCC, and is associated with HPV16 infection in CINs. Lymph node metastasis and parametrial invasion are poor prognostic factors for SCC, while positive E-cadherin expression may serve as a protective prognostic factor for SCC.