Expression of bcl-2 and bax in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix

Bcl-2 protein together with the pro-apoptotic protein bax, are thought to function by forming homo- and heterotypic dimers which control the progression to apoptosis. In this immunohistochemical study we investigated the expression of bcl-2 and bax apoptosis related proteins in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Twenty-four cervical intraepithelial neoplasias grade 1-2 (CIN I/II), 38 grade 3 (CIN III), and 53 invasive squamous cell carcinomas (ISCC) were investigated by immunohistochemical staining for bcl-2 and bax protein. Bcl-2 immunoreactivity was found in five of the 24 CIN I/II cases (20.8%), 18 of 38 CIN II cases (47.4%) and nine of 53 ISCC cases (17%). The positivity for CIN III was significantly higher than for CIN I/II or ISCC (p=0.0351 and p=0.0018, respectively). The percentage of bax immunopositivity was somewhat higher in CIN III than in CIN I/II but this slight difference was not statistically significant. Correlation of the immunostaining results with tumor grade revealed a significant difference for bcl-2 which was more frequently immunopositive in well-differentiated tumors than in poorly-differentiated tumors. There was no significant relation between bax expression and tumor differentiation. Our results suggest that alterations of bcl-2 and bax expression may occur as a relatively early event in cervical tumorigenesis.