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Study on pathogenesis of endometrial carcinomas based on the analysis of growth and differentiation of endometrial gland

从子宫内膜腺生长分化分析子宫内膜癌发病机制

基本信息

批准号：
03670781
负责人：
KONISHI Ikuo
金额：
$ 1.34万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670781/
关键词：
endometrium endometrial carcinoma sex steroid receptor c-erbB-2 protein EGFR p53 C-erbB-2 protein 内膜癌 estrogen receptor(ER)progesterone receptor(PR)cーerb Bー2 protein

项目摘要

To verify the pathogenesis of endometrial carcinomas, expression of growth and differentiation factors such as sex steroid receptors (estrogen receptor; ER, progesterone receptors; PR), peptide growth factor receptors (c-erbB-2 protein, epidermal growth factor receptor; EGFR), and antioncogene product p53, has been studied immunohistochemically in normal, hyperplastic, and carcinomatous endometra. In normal endometrial glands, ER and PR are strongly expressed in the proliferative phase, but are down- regulated during the secretory phase. In contrast, hyperplastic and carcinomatous endometria exhibit constitutive expression of ER and/or PR, which is expressed in 70% cases of endometrial carcinomas. Normal endometrial stromal cells express PR throughout the menstrual cycle, whereas stromal cells surrounding carcinomatous glands are PR negative in 70% cases. Therefore, abnormal expression of ER and/or PR in both glandular and stromal cells may be one of the characteristics of early neoplastic change of endometrial tumorigenesis. In normal endometrium, c- erbB-2 protein is expressed exclusively in glandular cells but EGFR is mainly associated with stromal cells. Most endometrial carcinomas exhibit the expression pattern of c-erbB-2 protein positive and EGFR negative, but advanced and/or poorly differentiated carcinomas express both c-erbB-2 protein and EGFR. This suggests that EGFR expression is associated with progression of endometrial carcinomas. Normal endometrial glands do not express p53, and only 16.5% cases of endometrial carcinomas express p53. p53-positive tumors tend to develop in older postmenopausal women, and show non-endometrioid histology without ER and PR expression. Therefore, p53 gene alteration may be associated with estrogen-unrelated carcinomas.

为了证实子宫内膜癌的发病机制，生长和分化因子如性类固醇受体（雌激素受体; ER，孕激素受体; PR），肽生长因子受体（c-erbB-2蛋白，表皮生长因子受体; EGFR）和抗癌基因产物p53的表达，已在正常，增生和癌变子宫内膜中进行了化学研究。在正常子宫内膜腺体中，ER和PR在增殖期强表达，但在分泌期下调。相反，增生性和癌性子宫内膜呈现ER和/或PR的组成性表达，其在70%的子宫内膜癌病例中表达。正常子宫内膜间质细胞在整个月经周期中表达PR，而癌腺体周围的间质细胞在70%的病例中PR阴性。因此，ER和/或PR在子宫内膜腺细胞和间质细胞中的异常表达可能是子宫内膜肿瘤发生的早期癌变特征之一。在正常子宫内膜中，c-erbB-2蛋白仅表达于腺细胞，而EGFR主要表达于间质细胞。大多数子宫内膜癌c-erbB-2蛋白阳性，EGFR阴性，但晚期和/或低分化癌c-erbB-2蛋白和EGFR均表达。这表明EGFR表达与子宫内膜癌的进展有关。正常子宫内膜腺体不表达p53，只有16.5%的子宫内膜癌病例表达p53。p53阳性肿瘤倾向于发生在绝经后的老年妇女，并且显示非类胶质瘤组织学，没有ER和PR表达。因此，p53基因的改变可能与雌激素无关的癌有关。