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

为探讨子宫内膜癌的发病机制，用免疫组织化学方法研究了性激素受体(雌激素受体；ER、孕激素受体；PR)、多肽生长因子受体(c-erbB-2蛋白、表皮生长因子受体；EGFR)和抑癌基因产物P53等生长分化因子在正常子宫内膜、子宫内膜增生症和子宫内膜癌中的表达。在正常子宫内膜腺中，ER和PR在增生期表达较强，但在分泌期表达下调。相反，增生性和癌性子宫内膜显示ER和/或PR的组成性表达，70%的子宫内膜癌表达ER和/或PR。正常子宫内膜间质细胞在整个月经周期中都表达PR，而癌腺周围的间质细胞70%为PR阴性。因此，ER和/或PR在腺体和间质细胞中的异常表达可能是子宫内膜癌变的早期特征之一。在正常子宫内膜中，c-erbB-2蛋白仅在腺体细胞中表达，而EGFR主要与间质细胞有关。大多数子宫内膜癌c-erbB-2蛋白阳性，EGFR阴性，但进展期和/或低分化癌同时表达c-erbB-2蛋白和EGFR。这表明EGFR的表达与子宫内膜癌的进展有关。正常子宫内膜腺不表达P53，子宫内膜癌中仅16.5%表达P53。P53阳性肿瘤倾向于发生在老年绝经后妇女，表现为无ER和PR表达的非子宫内膜样癌。因此，P53基因的改变可能与雌激素无关的癌症有关。

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.