Apoptosis and the expression of Bax and Bcl-2 in hyperplasia and adenocarcinoma of the uterine endometrium

Apoptosis plays a crucial role in carcinogenesis in various tumours. This s tudy was designed to investigate the occurrence of apoptosis and the expres sion of Bcl-2 and Bax proteins in endometrial tumours of corpus uteri. METH ODS: Endometrial tissues were obtained from 20 patients with endometrioid a denocarcinoma, 16 patients with endometrial hyperplasia, and 4 patients wit h myoma uteri (which were used as controls). The occurrence of apoptosis wa s examined by using molecular biochemical techniques. The expression of Bcl -2 and Bax proteins was also investigated using immunohistochemical stainin g with appropriate antibodies. RESULTS: The labelling of DNA in situ indica ted that apoptotic cells were sporadically seen in postmenopausal endometri um (5.2 +/- 2.1, n = 4) and endometrial hyperplasia without atypia (2.6 +/- 0.5, n = 9). In contrast, labelled cells were detected in atypical endomet rial hyperplasia (15.9 +/- 2.2, n = 7), and their numbers increased intense ly in adenocarcinoma (29.3 +/- 3.7, n = 20). Autoradiographic analysis reve aled DNA laddering in many cases of carcinoma. Bcl-2 was highly immunoposit ive in hyperplasia without atypia (36.2 +/- 6.5%, n = 9), but was decreased in the atypical endometrial hyperplasia (16.3 +/- 4.8%, n = 7). Large frac tions of the carcinoma (6.3 +/- 1.8%, n = 20) and normal endometrium (2.8 /- 1.4%, n = 4) were immunonegative or slightly immunopositive to Bcl-2. In contrast, Bax immunoreactivity was more frequent and stronger in adenocarc inoma (43.6 +/- 4.1%, n = 20) than that in normal endometrium (17.6 +/- 6.7 %, n = 4) and hyperplasia (7.2 +/- 2.2%, n = 16). CONCLUSIONS: These result s suggest that cells in hyperplasia expressing Bcl-2 might have prolonged s urvival ability. Neoplastic cells in adenocarcinoma might show apoptosis in association with a decreased expression of Bcl-2 and an increased expressi on of Bax. Therefore, the frequency of apoptosis and the expression of Bcl- 2 and Bax might be correlated with carcinogenesis in the uterine endometriu m of humans.