ESTROGEN AND PROGESTERONE RECEPTOR EXPRESSION IN TRACHEAL MUCOSA OF PATIENTS WITH IDIOPATHIC SUBGLOTTIC STENOSIS

Abstract

TOPIC: Lung Pathology TYPE: Original Investigations PURPOSE: Idiopathic subglottic stenosis (iSGS) is the narrowing of subglottic space without antecedent injury or identifiable disease process, that leads to airway stenosis. The causative mechanism and pathogenesis remains unclear. The purpose of this pilot study is to evaluate the role of estrogen and progesterone in the pathophysiology of iSGS as it almost exclusively effects females. METHODS: We performed a prospective case control study of patients with iSGS undergoing endoscopic dilation procedures. Patients were identified using the departmental registry for iSGS patients. Patients without a diagnosis of iSGS undergoing bronchoscopy for non-dilation procedures served as controls and iSGS patients served as self controls. Endobronchial forceps biopsies were obtained from the stenotic area in iSGS patients and normal tracheal mucosa distal to the stenotic area. In controls, endobronchial forceps biopsies were obtained from normal tracheal mucosa. The specimens were stained for estrogen alpha and progesterone receptors.We assessed the estrogen alpha and progesterone receptor status of the specimens with plans for estrogen beta testing in the future. We avoided direct comparison due to relatively small numbers. RESULTS: Histological samples of 13 patients with iSGS and 7 controls were evaluated (Table 1). Patients with iSGS had undergone at least 1 endoscopic dilation prior to inclusion. 7 patients were included as controls, 3/7 with sarcoidosis, 3/7 with suspected lung cancer and 1/6 with tracheobronchomalacia.Significantly more fibrosis and chronic inflammation was identified in the iSGS specimens compared with the non-stenotic areas and control samples (Table 1). Mucosal ulceration and acutely inflamed granulation tissue (5 of 13 patients), squamous metaplasia (9 of 13 patients), were seen only in stenotic areas. Samples from the patient’s normal mucosa expressed mild and moderate estrogen alpha (90%). In contrast 61% of the peri-stenotic samples were negative. The PR expression showed moderate and high expression in the biopsies of non-involved areas (87.5%), but was significantly decreased to no or low levels (90%) in the peri-stenotic samples. In each patient, the expression of ER alpha and progesterone receptors were decreased in the peri- stenotic compared with the non-stenotic areas. CONCLUSIONS: The predilection of iSGS for premenopausal females is suggestive of hormonal causality. This pilot study suggests that iSGS patients may have higher levels of hormone receptors, compared with the general population. In addition, the expression of hormone receptors, especially progesterone, is decreased in the peri-stenotic areas. Further studies with a larger population are needed to identify the role of hormones, and potential use of hormone receptor therapy for altered expression of these receptors. DISCLOSURES: No relevant relationships by Valentina Robila, source=Web Response No relevant relationships by javeryah safi, source=Web Response Consultant relationship with COOK medical Please note: $1001 - $5000 by Ray Shepherd, source=Web Response, value=Consulting fee Royalties - authorship relationship with UpToDAte Please note: $1001 - $5000 by Ray Shepherd, source=Web Response, value=Royalty grant for industry study relationship with Olympus Spiration Please note: $1001 - $5000 by Ray Shepherd, source=Web Response, value=Grant/Research Support