EVALUATION OF THE RISK OF CERVICAL INTRAEPITHELIAL NEOPLASIA PROGRESSION BASED ON CELL PROLIFERATION INDEX, EPITHELIAL-MESENCHYMAL TRANSITION AND CO-INFECTIONS.

Human papilloma virus (HPV) infection, especially with high risk types, represent the major etiological factor for the development of cervical precancerous and cancerous lesions. However, other factors including cell proliferation index, epithelial-mesenchymal transition and the presence of co-infections might also influence the progression of cervical intraepithelial neoplasia (CIN). The aim of our study was to analyse, the expression of cell proliferation markers and epithelial-mesenchymal transition markers during the progression of cervical intraepithelial neoplasia, in cases with and without co-infections. Standard immunohistochemistry was used to detect, Ki67, cyclin D1, phosphohiston-H3, p63, E-cadherin, β-catenin and vimentin. The results of our study indicated that the expression of Ki67, phosphohiston-H3 and p63 is significantly increased during the progression of CIN disease, whilst the expression of E-cadherin and β-catenin are progressively lost. The expression of mesenchymal marker vimentin is also increased in CINIII and in invasive carcinoma. Proliferation index based on Ki67 labelling is significantly higher in cases with co-infections and the expression on E-cadherin is significantly lower in cases with co-infections compared to cases without co-infections. In conclusion, the measurement of proliferation index, based on Ki67 labelling, as well as mitotic index based on phosphohiston-H3 detection can reliably indicate high and low risk groups of the progression of CIN. Similarly, higher p63 expression, loss of E-cadherin and β-catenin and higher vimentin expression can indicate the progression risk of CIN. The presence of co-infections is associated with the increased expression of proliferation marker Ki67 and the loss of E-cadherin and therefore it can be considered as an additional marker of CIN progression.