Apotosis-related Proteins in Cervical Intraepithelial Neoplasia and Squamous Cell Carcinoma of the Cervix

Objectives: A loss of balance between proliferation and apoptosis leads to tumor formation. Normal cervical epithelium becomes dysplastic before potentially developing into carcinoma. This study was conducted to delineate the role of apoptosis-related proteins in various stages of development in cervical neoplasia. Both regulator and effector proteins were examined.

Methods: The expression of apoptosis-related proteins, including five members of the Bcl-2 family and two members of the caspase family, was evaluated in 26 low-grade cervical intraepithelial neoplasias (CIN-L), 37 high-grade cervical intraepithelial neoplasias (CIN-H), and 43 cervical squamous cell carcinomas, using immunohistochemistry. Specimens showing cytosolic immunoreactivity in 10% or more of the neoplastic cells were considered immunopositive.

Results: One hundred six subjects were studied. All seven apoptotic regulators examined were positive in a proportion of these neoplasms. The expression of Caspase 3 was significantly higher in CIN-H than in CIN-L (P = 0.016). The expression of Bak, Caspase 3, and Caspase 6 was reduced in cervical carcinoma compared to CIN-H (P < 0.01, P = 0.026, P < 0.01, respectively).

Conclusions: There is an increase in expression of Caspase 3 in CIN-H compared to CIN-L and the increase is thought to be related to the increased proliferative activity in dysplastic cells. The reduction of Bax, Caspase 3, and Caspase 6 expression in carcinoma indicates that the apoptotic mechanism has become defective in the process of malignant transformation.