Fas-mediated pathway and apoptosis in normal, hyperplastic, and neoplastic endometrium

Abstract

Introduction. Abnormalities in the control of cell proliferation and apoptosis have been suggested to contribute to the development and progression of neoplasia. There are at least two pathways that activate apoptosis. The first is a mitochondria-dependent route governed by bcl-2 family proteins. The second is a parallel mechanism which involves the activation of a group of tumor necrosis factor (TNF) receptors, such as Fas. Aims. The aim of this study was to examine the distribution and interrelation between the expression patterns of apoptosis-related proteins such as Fas, caspase-3 (CPP32), and M30, and to investigate the role of Fas-mediated apoptosis in the pathogenesis and progression of endometrial neoplasms. Materials and methods. Using specific antibodies for Fas, caspase-3, and M30, we examined protein expressions in 29 endometrial carcinomas, 30 endometrial hyperplasias, and 21 normal cyclic endometria. The results of immunostaining for Fas and caspase-3 were analyzed semiquantitatively by using an immunohistochemical scoring system (HSCORE) that incorporated both the intensity and the distribution of specific staining. For M30, positive staining cells and extracellular particles were analyzed semiquantitatively per 10 high-power fields. Results. HSCOREs of Fas and caspase-3 were slightly higher in the secretory endometria than in the proliferative endometria. Similarly, M30 reactivity seemed to increase in the late secretory phase of the cycle. HSCOREs of Fas and caspase-3 and the reactivity of M30 were significantly higher in the carcinoma group than in the simple hyperplasia group (P < 0.05). Complex hyperplasias, however, expressed quite similar HSCOREs of Fas and caspase-3 as carcinomas. M30 reactivity was also significantly higher in complex hyperplasias than in simple hyperplasias, and in carcinomas positivity increased significantly (P < 0.05) as the grade progressed. Conclusions. The significant increase observed in Fas, caspase-3, and M30 expression in carcinomas as compared with simple hyperplasias may suggest that the Fas-related apoptotic pathway is also involved in the regulation of apoptosis in the endometrial tissue and promotes the development and progression of endometrial neoplasia. (C) 2003 Elsevier Inc. All rights reserved.