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 young women, is characterized by proliferation of abnormal smooth muscle cells (LAM cells), which often differ from normal pulmonary smooth muscle cells by frequently having estrogen and progesterone receptors.


OBJECTIVE
To evaluate the relationships among several factors related to proliferation and apoptosis in LAM cells, we employed immunohistochemical methods for the localization of Bcl-2 and Mcl-1 (inhibitors of apoptosis), Bax (a promoter of apoptosis), c-Myc (an apoptosis-related oncoprotein), proliferating cell nuclear antigen (an indicator of mitotic activity), and nick end labeling (to identify apoptotic cells) in lung tissues of 9 patients with LAM.


RESULTS
In all patients, most LAM cells reacted positively for Bax. The LAM cells were positive for both Bcl-2 and estrogen receptor in 5 patients, positive for only Bcl-2 in 1 patient, positive for only estrogen receptor in another patient, and negative for both in 2 patients. More than 50% of the Bcl-2-positive LAM cells were also positive for estrogen receptor. The reaction for c-Myc was positive in all patients. The immunoreactivity for Bcl-2 and Mcl-1, which inhibit apoptosis, was more intense in LAM cells than in normal vascular and bronchial smooth muscle cells. In 6 patients, more than 50% of the LAM cells were positive for proliferating cell nuclear antigen. Apoptosis was infrequent in LAM cells.


CONCLUSIONS
Our results suggest that the expression of Bcl-2 in LAM cells may be related to hormonal regulation, and that by decreasing apoptosis, Bcl-2 and related proteins contribute to the imbalance between proliferation and death of LAM cells.
Usuki
J
J
Pathology Section, Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1518, USA.
Horiba
K
K
Chu
S C
SC
Moss
J
J
Ferrans
V J
VJ
D000328:Adult; D016923:Cell Death / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000737:chemistry* / Q000473:pathology; D008203:Lymphangiomyoma / Q000737:chemistry* / Q000473:pathology; D008875:Middle Aged; D008938:Mitosis / Q000502:physiology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000032:analysis*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D011956:Receptors, Cell Surface / Q000032:analysis*; D013194:Staining and Labeling; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; D051028:bcl-2-Associated X Protein