IMMUNOHISTOCHEMICAL ANALYSIS OF PROTEINS OF THE BCL-2 FAMILY IN PULMONARY LYMPHANGIOLEIOMYOMATOSIS - ASSOCIATION OF BCL-2 EXPRESSION WITH HORMONE-RECEPTOR STATUS

Background.-Pulmonary lymphangioleiomyomatosis (LAM), a disease of you ng women, is characterized by proliferation of abnormal smooth muscle cells (LAM cells) which often differ from normal pulmonary smooth musc le cells by frequently having estrogen and progesterone receptors. Obj ective.-To evaluate the relationships among several factors related to proliferation and apoptosis in LAM cells, we employed immunohistochem ical methods for the localization of Bcl-2 and Mcl-1 (inhibitors of ap optosis), Bax (a promoter of apoptosis), c-Myc (an apoptosis-related o ncoprotein), proliferating cell nuclear antigen (an indicator of mitot ic activity), and nick end labeling (to identify apoptotic cells) in l ung tissues of 9 patients with LAM. Results.-In all patients, most LAM cells reacted positively for Bax. The LAM cells were positive for bot h Bcl-2 and estrogen receptor in 5 patients, positive for only Bcl-2 i n 1 patient, positive for only estrogen receptor in another patient, a nd negative for both in 2 patients. More than 50% of the Bcl-2-positiv e LAM cells were also positive for estrogen receptor. The reaction for c-Myc was positive in all patients. The immunoreactivity for Bcl-2 an d Mcl-1, which inhibit apoptosis, was more intense in LAM cells than i n normal vascular and bronchial smooth muscle cells. In 6 patients, mo re than 50% of the LAM cells were positive for proliferating cell nucl ear antigen. Apoptosis was infrequent in LAM cells. Conclusions.-Our r esults suggest that the expression of Bcl-2 in LAM cells may be relate d to hormonal regulation, and that by decreasing apoptosis, Bcl-2 and related proteins contribute to the imbalance between proliferation and death of LAM cells.