Ashihara Koji, Saito Tsuyoshi, Mizumoto Hisanobu, Nishimura Makoto, Tanaka Ryoichi, Kudo Ryuichi
Department of Obstetrics and Gynecology, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo 060-0061, Japan.
Med Electron Microsc. 2002 Mar;35(1):9-15. doi: 10.1007/s007950200001.
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.
子宫内膜增生是雌激素过度刺激或无对抗性刺激的一种公认后果，被认为是子宫内膜腺癌的一种癌前病变。我们之前已经表明，β-连环蛋白在人子宫内膜中的亚细胞定位会根据细胞增殖情况发生变化，这表明细胞间转导在人子宫内膜细胞生长控制中发挥作用，不仅在生理状态下如此，在致癌的子宫内膜中也是如此。在本研究中，为了阐明β-连环蛋白基因的分子改变发生在子宫内膜癌发生的哪个阶段，我们通过免疫组织化学分析了β-连环蛋白的亚细胞定位，并分别分析了25例子宫内膜增生患者和20例与子宫内膜增生相关的子宫内膜癌患者的β-连环蛋白基因外显子3，从癌组织和增生组织中提取DNA进行分析。25例子宫内膜增生样本中有14例（56.0%）、20例与增生相关的子宫内膜癌中有12例（60.0%）以及这些癌症相关的增生组织中有11例（55.0%）显示β-连环蛋白的核定位。在20例子宫内膜癌样本中有2例发现β-连环蛋白基因外显子3发生突变；然而，在25例子宫内膜增生或20例相关增生组织中未发现该突变。结果表明，在子宫内膜癌发生过程中，β-连环蛋白基因的分子改变发生在非典型增生或癌症阶段，而非无非典型性的单纯或复杂性增生阶段。
