|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1992 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1991 : ¥1,200,000 (Direct Cost : ¥1,200,000)
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 neopla
stic 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.
一方、内膜癌患者の中には、ときにunopposed estrogenの関与が全く考えられないような症例が存在している。すなわち、閉経後長期間を経た肥満も認めないような患者で、組織型はpapillary serous carcinomaやclear cell carcinomaなどのようなnon-endometriodtypeのものが多く、これらの腫瘍細胞は性ステロイド受容体を発現していない場合が多い。今回の研究では、これらのestrogen-unrelatedな内膜癌にp53遺伝子異常が存在している可能性が強く示唆された。 Less