Downregulation of estrogen and progesterone receptors in the abnormal smooth muscle cells in pulmonary lymphangioleiomyomatosis following therapy. An immunohistochemical study.
Immunohistochemical and confocal microscopic studies were made on lung tissue from 10 women with lymphangioleiomyomatosis (LAM) to evaluate the distribution of estrogen receptors (ER) and progesterone receptors (PR) in the abnormal smooth muscle cells (LAM cells) that characterize this disorder. PR and ER were localized mainly in the nuclei of large, epithelioid LAM cells, in five patients in whom tissues were obtained before treatment. However, the reaction for PR and ER was essentially negative in similarly processed tissues from five patients studied after receiving hormonal therapy (progesterone and tamoxifen). In the untreated group, staining for ER and PR colocalized with that for HMB-45, but not with that for membrane type-1 matrix metalloproteinase (MT-1-MMP), which we have shown to be localized in proliferating LAM cells. These observations demonstrate that PR and ER are selectively expressed in a subpopulation of LAM cells that are larger in size, have a limited ability to proliferate, and do not produce MT-1-MMP, the enzyme that activates MMP-2 (which is secreted by LAM cells and is capable of lysing elastin and collagens). ER and PR in LAM cells appear to be downregulated by hormonal therapy.
Matsui
K
K
Pathology Section and Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1518, USA.
Takeda
K
K
Yu
Z X
ZX
Valencia
J
J
Travis
W D
WD
Moss
J
J
Ferrans
V J
VJ
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018192:Lymphangioleiomyomatosis / Q000188:drug therapy* / Q000473:pathology; D018613:Microscopy, Confocal; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D011374:Progesterone / Q000627:therapeutic use; D011960:Receptors, Estrogen / Q000187:drug effects*; D011980:Receptors, Progesterone / Q000187:drug effects*; D013629:Tamoxifen / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D011374:Progesterone