The Patterns of Expression of an Apoptosis-Related CK18 Neoepitope, the bcl-2 Proto-Oncogene, and the Ki67 Proliferation Marker in Normal, Hyperplastic, and Malignant Endometrium

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Abstract
Expression of a neoepitope on cytokeratin 18, recognized by the monoclonal antibody M30, is an early indicator of apoptosis in epithelial cells. The aim of this study was to determine the equilibrium between apoptosis (M30), anti-apoptosis (bcl-2), and proliferation (Ki-67) in different endometrial conditions. Paraffin-embedded samples (n = 107), representing proliferative endometrium (18), secretory endometrium (19), postmenopausal endometrium (15), disordered proliferative endometrium (6), simple hyperplasia (12), complex hyperplasia (8), and endometrial adenocarcinoma (29), were evaluated immunohistochemically. The indirect streptavidin-biotin-horseradish peroxidase technique, with 3-amino-9-ethylcarbazole as the chromogen, was used to visualize the reactions. Proliferative endometrium showed high bcl-2 and Ki-67 expression levels with no M30. In the secretory phase, the balance was tipped in favor of M30 with a decrease of bcl-2 and Ki-67. Postmenopausal endometrium revealed high Ki-67 and bcl-2 expression levels and no M30. In complex hyperplasia, M30, bcl-2, and Ki-67 showed increased expression. In endometrial carcinoma, an increasing reactivity for M30 and Ki-67 was seen as the grade progressed. bcl-2 reacted weakly and only in grade 1 cancer. Immunohistochemistry facilitates the study of the expression of proteins related to cyclic endometrial activity. Interruption of these cyclic events is associated with specific disturbances in the expression patterns of these proteins.