title: Sex steroid receptor expression in idiopathic pulmonary fibrosis.
abstract: Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF.
authors.affiliation: University of Pittsburgh Medical Center, Presbyterian Hospital, Department of Pathology, Pittsburgh, PA 15213; Vanderbilt University Medical Center, Department of Pathology, Microbiology and Immunology, Nashville, TN, 37232. Electronic address: mitra.mehrad@vanderbilt.edu.
authors.forename: Mitra
authors.initials: M
authors.lastname: Mehrad
authors.affiliation: University of Pittsburgh Medical Center, Presbyterian Hospital, Department of Pathology, Pittsburgh, PA 15213.
authors.forename: Humberto E
authors.initials: HE
authors.lastname: Trejo Bittar
authors.affiliation: University of Pittsburgh Medical Center, Presbyterian Hospital, Department of Pathology, Pittsburgh, PA 15213.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Yousem
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000032:analysis; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000737:chemistry / Q000473:pathology; D011651:Pulmonary Artery / Q000737:chemistry / Q000473:pathology; D011667:Pulmonary Veins / Q000737:chemistry / Q000473:pathology; D011944:Receptors, Androgen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis*; D012189:Retrospective Studies
chemical_list: C410798:AR protein, human; D015415:Biomarkers; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen; D011980:Receptors, Progesterone
keywords: Idiopathic pulmonary fibrosis; Lung; Progesterone receptor; Sex steroid receptor; Usual interstitial pneumonia