Apoptosis and the expression of Bax and bcl-2 in squamous cell carcinoma and adenocarcinoma of the uterine cervix

Abstract

Apoptosis plays a crucial role in the suicide and turnover of cells in various tumors. This study was designed to investigate the relation between apoptosis and the histologic types of cell in invasive cervical carcinoma. Cervical tissues were obtained from 19 patients with invasive squamous cell carcinoma (ISCC), 9 patients with invasive endocervical adenocarcinoma (IEAC), and 15 patients with myoma uteri (which were used as controls). Each tissue was rapidly frozen and/or fixed in Bouin's solution. The occurrence of apoptosis was examined by end labeling of DNA with (alpha-32P)dideoxyATP and electrophoretic fractionation and by end labeling of DNA in situ with digoxigenin-dideoxyUTP. The expression of Bcl-2 and Bax proteins was examined by immunohistochemical staining with appropriate antibodies. Autoradiographic analysis revealed that high molecular weight DNA was predominant in the normal cervical epithelium (NCE) and in ISCC. However, a ladder-like pattern of DNA fragments, characteristic of the apoptotic breakdown of DNA, was identified in IEAC. Quantitative analysis of low molecular weight fragments of DNA revealed a significant increase in IEAC but not in ISCC compared with NCE. Labeling of DNA in situ indicated that cells undergoing apoptosis were predominant among the neoplastic cells of IEAC. However, no apoptotic cells were noted in ISCC, with the exception of cells in some tumor nests. A large fraction of IEAC and ISCC was immunonegative for Bcl-2. Although the expression of Bax was detected weakly in a small fraction of ISCC, strong expression of Bax was observed in all cases of IEAC. Apoptosis appears to occur in the cancerous cells of invasive adenocarcinoma of the uterine cervix in association with a high level of expression of Bax but not of bcl-2.