Morphology, molecular regulation and significance of apoptosis in pituitary adenomas

Apoptosis represents energy-requiring spontaneous single cell death, with specific morphologic and biochemical features. It is a rapidly processed sequence of events resulting in elimination of damaged cells. Apoptosis occurs in physiological remodeling and proliferative conditions, and also in neoplastic lesions. Several molecules and molecular systems such as bet-2/bax, Fas/FasL and caspases regulate the apoptotic process. Apoptosis is characterized by a stereotypic pattern of morphologic features, which can be illustrated mostly by electron microscopy. DNA and biochemical assays, based on the specific pattern of nucleosomal fragmentation can detect apoptosis. The in situ labeling techniques are currently used to demonstrate apoptosis in paraffin sections. Several studies of pituitary animal models, cell lines and human pituitaries have been performed during the last 6 years. By electron microscopy, pituitary adenoma cells undergoing apoptosis exhibit a common prototypical pathway of changes. Although the results by the situ labeling techniques are not uniform, apoptosis occurs with low frequency in a subset of pituitary adenomas, ill carcinomas and in pituitary hyperplasia. Alternative techniques based on remodeling of cytoskeleton by caspase activity can identify early apoptotic stages. This review presents the principles of apoptosis and summarizes the morphologic and functional changes of apoptosis in pituitary. Copyright (C) 2004 S. Karger AG, Basel.