Apoptosis and the expression of Bax and Bcl-2 in hyperplasia and adenocarcinoma of the uterine endometrium.
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.
Kokawa
K
K
Department of Obstetrics and Gynecology, Wakayama Medical University, 811-1 Kimidera, Wakayama 641-0012, Japan. katsu@wakayama-med.ac.jp
Shikone
T
T
Otani
T
T
Nishiyama
R
R
Ishii
Y
Y
Yagi
S
S
Yamoto
M
M
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D017209:Apoptosis; D053938:DNA Fragmentation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004717:Endometrium / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013194:Staining and Labeling; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein