Endometrial carcinoma arid gene mutation in relation to its carcinogenesis and prognosis

本研究的目的是阐明基因突变及其表达与子宫内膜癌的关系以及与肿瘤发生和预后的关系。材料为手术组织学标本和体外细胞系。1) VEGF表达与p53表达相关。将野生p53基因转染到p53突变的HEC-50B细胞中，VEGF表达下调。2) P53突变细胞中P53表达升高，标记指数大于45%提示存在突变。3)细胞周期调节因子Ki-67、Cyclins E、D1、A、PTEN的表达与高级别子宫内膜癌相关，而p14^<ARF>在低级别子宫内膜癌中呈负相关。几乎所有调控因子的表达都是相互关联的。在增生子宫内膜中，cyclin D1、A和PTEN的表达高于正常子宫内膜，但低于癌内膜。相比之下，细胞周期蛋白E在增生中不表达。4) P27在增殖期不表达，而在秘书期表达。在恶性肿瘤中，它在高级别肿瘤中表达更强烈，似乎失去了抑制生长的功能。p27的失活因子Skp2在高级别癌中被激活。在具有PR升高p27的高分化癌细胞（HEC-265）中，当给予黄体酮时，保留正常子宫内膜的反应性。在接受黄体酮治疗的有效组中，p27的表达在治疗13周后持续存在。P27可作为黄体酮治疗效果的预测指标。

The aim of the study is to clarify the correlation of gene mutation and its expression with endometrial carcinoma in relation to carcinogenesis and prognosis of the tumor. The materials are the surgical histology specimens and cell lines in vitro.1) VEGF expression is correlated with p53 expression. When wild p53 gene was transfected into p53-mutated HEC-50B cells, VEGF expression was down regulated.2) P53 expression was elevated in p53-mutated cells and labeling index more than 45% indicated existence of the mutation.3) Expressions of cell cycle regulators, including Ki-67, Cyclins E, D1, A and PTEN were correlated with those of higher-grade endometrial carcinoma, whereas p14^<ARF> was inversely higher in low grade. Expressions of almost all regulators were correlated from each other. In hyperplasia, cyclin D1, A and PTEN were expressed more intensively than normal endometrium, but less than carcinoma. In contrast, cyclin E was not expressed in hyperplasia.4) P27 did not express in proliferative phase, but in secretary phase. In carcinomas, it expressed more intensively in higher grade, seemingly loosing growth-suppressive function. Skp2, inactivating factor of p27, was activated in high-grade carcinoma. In well-differentiated carcinoma cells (HEC-265) that possess PR elevated p27, when progestin was given, preserving the reactivity of normal endometrium. In effective group of patients who had progestin therapy, p27 expression was persistent after 13 weeks of the therapy. P27 can be a predictor of effectiveness for progestin therapy.