Subject(s)
Endothelial Cells/cytology , Gene Expression Regulation, Neoplastic , Lymphangiomyoma/metabolism , Vascular Endothelial Growth Factor Receptor-3/metabolism , Cell Proliferation , Disease Progression , Humans , Immunohistochemistry , Lung/metabolism , Lung/pathology , Lymphangiomyoma/pathology , Neoplasm Metastasis , PhenotypeABSTRACT
We examined ten cases of extrapulmonary lymphangioleiomyoma/lymphangioleiomyomatosis (LAM; all patients female; median age 46.5 years) for immunohistochemical labeling with a monoclonal antibody against podoplanin (D2-40), which is specific for lymphatic endothelial lining. We found positive staining in thin-wall branching vessels reflecting the lymphatic nature of tumor vessels in all cases tested. In contrast, perivascular (HMB-45 positive) myoid cells were not detected by D2-40. The D2-40 labeling confirms the current concept of lymphangiogenic origin of the tumor vessels in LAM. In addition, this study makes a further contribution to the immunohistochemical mapping of this antibody in vascular tumors. Finally, the use of this commercially available antibody provides an additional help in the differential diagnosis of LAM from other soft tissue tumors.
Subject(s)
Antibodies, Monoclonal/analysis , Lymphangiomyoma/pathology , Membrane Glycoproteins/analysis , Vascular Neoplasms/pathology , Actins/analysis , Adult , Aged , Antibodies, Monoclonal/immunology , Antigens, Neoplasm , Female , Humans , Immunohistochemistry , Lymphangiogenesis , Lymphangioleiomyomatosis/metabolism , Lymphangioleiomyomatosis/pathology , Lymphangiomyoma/metabolism , Lymphatic Vessels/chemistry , Lymphatic Vessels/pathology , Melanoma-Specific Antigens , Membrane Glycoproteins/immunology , Middle Aged , Muscle, Smooth/chemistry , Neoplasm Proteins/analysis , Platelet Endothelial Cell Adhesion Molecule-1/analysis , Vascular Neoplasms/metabolismABSTRACT
Estrogen and progesterone receptors were demonstrated immunocytochemically in the lung tissue of two cases of pulmonary lymphangioleiomyomatosis. In one case both receptors were localized in the proliferative smooth muscle nodules and diffusely in the interstitial tissue in close proximity to the muscle. The pulmonary tissue in the other case contained the estrogen receptor only. The authors conclude that the response to hormonal treatment seen in this disease might be optimized in the future by monitoring for the presence of steroid hormone receptors.
Subject(s)
Lung Neoplasms/metabolism , Lymphangiomyoma/metabolism , Lymphoproliferative Disorders/metabolism , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Adult , Antibodies, Monoclonal , Female , Humans , Immunoenzyme Techniques , Lung/metabolism , Lung/pathology , Lung Neoplasms/pathology , Lymphangiomyoma/pathologyABSTRACT
Abnormal proliferation of smooth muscle cells in pulmonary lymphangioleiomyomatosis (LAM) is thought to be influenced by estrogen and progesterone. However, the results of previous studies using cytosolic methods to measure estrogen and progesterone receptor content in lung tissue from these patients have been inconsistent. We used immunohistochemical methods to study the tissue distribution of estrogen and progesterone receptors in LAM as well as in smooth muscle of several other organs, including histologically normal lung, colon, bladder, prostate, uterus, and uterine leiomyomas. Progesterone receptor was expressed strongly and estrogen receptor more weakly by the abnormal myoid cells of LAM. Hormone receptors were absent from all other constituents of lung tissue in our patient. These findings were similar to those in histologically normal myometrium and uterine leiomyomas. Although we found focal labeling of prostatic stromal cells with anti-progesterone receptor, no other smooth muscle tissue expressed either estrogen or progesterone receptor. We conclude that LAM is an abnormal proliferation of smooth muscle cells that express both estrogen and progesterone receptors.
Subject(s)
Lung Neoplasms/ultrastructure , Lymphangiomyoma/ultrastructure , Receptors, Steroid/metabolism , Female , Humans , Immunohistochemistry , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lymphangiomyoma/metabolism , Lymphangiomyoma/pathology , Lymphoproliferative Disorders , Middle Aged , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolismABSTRACT
Pulmonary lymphangiomyomatosis is a rare disease characterized by wide-spread proliferation of smooth muscle cells around lymphatic and blood vessels, smaller airways and in the interstitium. Young women in the fertile status are almost exclusively affected. Spontaneous recurrent pneumothorax is the most important symptom. Chylous effusions are reported in 37.5% of cases. Our observation deals with a woman aged 43. Light- and electron-microscopic findings are described. Estrogen receptors have been detected on smooth muscle cells. Bilateral oophorectomy and treatment with progesterone were successful.
Subject(s)
Lung Neoplasms/pathology , Lymphangiomyoma/pathology , Lymphoproliferative Disorders/pathology , Adult , Cell Transformation, Neoplastic/pathology , Desmin/metabolism , Female , Humans , Immunohistochemistry , Lung Neoplasms/metabolism , Lung Neoplasms/ultrastructure , Lymphangiomyoma/metabolism , Lymphangiomyoma/ultrastructure , Microscopy, Electron , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Muscle, Smooth, Vascular/ultrastructure , Neoplasms, Hormone-Dependent/ultrastructure , Receptors, Estrogen/analysisABSTRACT
As an initial step in investigating the role of steroid hormones in lymphangiomyomatosis, the cytosolic receptors for steroid hormones were determined by a dextran charcoal method. Specific saturable receptors were found for estrogens (measured with [3H] estradiol +/- unlabeled diethylstilbestrol), progestins (measured with [3H] R5020 +/- unlabeled R5020), and glucocorticoids (measured with [3H] dexamethasone +/- unlabeled dexamethasone); they were absent for androgens (measured with [3H] R1881 +/- unlabeled R1881). Even though receptor levels were of low absolute value, they were significant because specimens of normal lung display no receptor at all. Steroid hormones may have direct effects on pulmonary lymphangiomyomatosis tissue mediated by specific receptors.
