Human Reproduction, Vol. 16, No. 10, 2211-2218,
October 2001
© 2001 European Society of Human Reproduction and Embryology
Apoptosis and the expression of Bax and Bcl-2 in hyperplasia and adenocarcinoma of the uterine endometrium
Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-0012, Japan
BACKGROUND: Apoptosis plays a crucial role in carcinogenesis in various tumours. This study was designed to investigate the occurrence of apoptosis and the expression of Bcl-2 and Bax proteins in endometrial tumours of corpus uteri. METHODS: Endometrial tissues were obtained from 20 patients with endometrioid adenocarcinoma, 16 patients with endometrial hyperplasia, and 4 patients with myoma uteri (which were used as controls). The occurrence of apoptosis was examined by using molecular biochemical techniques. The expression of Bcl-2 and Bax proteins was also investigated using immunohistochemical staining with appropriate antibodies. RESULTS: The labelling of DNA in situ indicated that apoptotic cells were sporadically seen in postmenopausal endometrium (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 endometrial hyperplasia (15.9 ± 2.2, n = 7), and their numbers increased intensely in adenocarcinoma (29.3 ± 3.7, n = 20). Autoradiographic analysis revealed DNA laddering in many cases of carcinoma. Bcl-2 was highly immunopositive 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 fractions 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 adenocarcinoma (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 results suggest that cells in hyperplasia expressing Bcl-2 might have prolonged survival ability. Neoplastic cells in adenocarcinoma might show apoptosis in association with a decreased expression of Bcl-2 and an increased expression of Bax. Therefore, the frequency of apoptosis and the expression of Bcl-2 and Bax might be correlated with carcinogenesis in the uterine endometrium of humans.
Key words: Apoptosis/Bax/Bcl-2/endometrial carcinoma/endometrial hyperplasia
1 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Wakayama Medical University,811–1 Kimiidera, Wakayama 641-0012, Japan. E-mail: katsu{at}wakayama-med.ac.jp
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