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Apoptosis plays one of the major roles in the progression of human cancers including cervical carcinoma. The aim of our study was to analyse the expression of Cas3, Bax and their correlation with the proliferation index and ER expression status during the progression of cervical intraepithelial neoplasia (CIN). Study included altogether 140 specimens, divided into two major groups, such as: cervical lesions without co-infections and with co-infections. Standard immunohistochemistry was used to detect antigens: Ki67, Cas3, Bax and ER. The study results showed that the expression of Cas3 is significantly decreased whilst the expression of Bax is significantly increased during the progression of CIN in both groups with and without co-infections. The expression of Bax negatively correlates with the expression of Cas3 (r=-42.4, p<0.05) and ER (r=-33.4, p<0.05) and positively correlates with the expression of proliferation marker Ki67 (r=56.3, p<0.05). The results indicate that the deregulated apoptosis measured as increased expression of Bax and Cas3 loss, as well as the increase in proliferation index measured as Ki67 expression is significantly related to the progression of CIN into cervical carcinoma. Therefore, the measuring of mentioned protein expression could be used as the markers of the CIN progression.

Stem cells represent the small subpopulation of healthy and cancerous tissues, which are characterised with increased proliferation and self-renewal properties. From the many different markers of stem cells, we have investigated the stem cell index during the progression of cervical intraepithelial neoplasia (CIN), based on the immunohistochemical expression of CD44 in total of 140 tissue samples from uterine cervix. In addition, we have performed the profound correlation analysis of CD44 with different epithelial-mesenchymal, proliferation, apoptosis and hormonal markers at both protein and mRNA level. The results of our study indicated that, stem cell index based on the CD44 detection is significantly increased with the progression of cervical intraepithelial neoplasia. In addition, CD44 expression significantly correlates with the epithelial-mesenchymal transition, proliferation-apoptotic features and ER status in both protein and mRNA level. Two, groups of cervical intraepithelial lesions as well as carcinoma can be identified based on the expression of CD44, Ki67, Cas3 and ER. To the best of our knowledge we are first to demonstrate such findings in CIN and cervical carcinoma and identified characteristics could be used for the early assessment of CIN patient prognosis and for the relevant clinical management.

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.