Mutation of beta-catenin gene in endometrial cancer but not in associated hyperplasia.
Endometrial hyperplasia is a recognized effect of excessive or unopposed estrogen stimulation and is considered to be a precancerous condition of endometrial adenocarcinoma. We have previously shown that the subcellular localization of beta-catenin in the human endometrium is changed according to cell proliferation, suggesting a role of intercellular transduction in cell-growth control in human endometrium, not only in the physiological condition but also in the carcinogenic endometrium. In the present study, to clarify at which stage of endometrial carcinogenesis molecular alteration of the beta-catenin gene occurs, we analyzed the subcellular localization of beta-catenin by immunohistochemistry, and we analyzed exon 3 of the beta-catenin gene, in 25 patients - with endometrial hyperplasia and 20 patients with endometrial cancers associated with endometrial hyperplasia, digesting DNA from the cancer and hyperplasia parts, separately. Fourteen of the 25 (56.0%) endometrial hyperplasia samples, 12 (60.0%) endometrial cancers, and 11 (55.0%) associated hyperplasias of the 20 endometrial cancers associated with hyperplasia showed nuclear localization of beta-catenin. Mutation in exon 3 of the beta-catenin gene was found in 2 of the 20 endometrial cancer samples; however, it was not found in the 25 endometrial hyperplasias or the 20 associated hyperplasias. The results suggest that molecular alteration of the beta-catenin gene occurs in atypical hyperplasia or cancer, rather than in simple or complex hyperplasia without atypia, during endometrial carcinogenesis.
Department of Obstetrics and Gynecology, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo 060-0061, Japan.
Koji
K
Ashihara
Tsuyoshi
T
Saito
Hisanobu
H
Mizumoto
Makoto
M
Nishimura
Ryoichi
R
Tanaka
Ryuichi
R
Kudo
D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004714:Endometrial Hyperplasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005091:Exons; D005260:Female; D006801:Humans; D016253:Microscopy, Immunoelectron; D017354:Point Mutation; D013347:Subcellular Fractions / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D015534:Trans-Activators; D051176:beta Catenin