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

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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.