Hormone receptors analysis in idiopathic progressive subglottic stenosis

Objective: Idiopathic subglottic stenosis predominantly affects fertile and perimenopausal women. Estrogens and/or progesterone have been proposed as mediators of its pathogenesis by stimulating collagen deposition within the upper airway. We evaluated the presence and expression of estrogen-alpha (ER-α), estrogen-beta (ER-β), and progesterone receptors (PR) in idiopathic stenotic patients. Study design: A retrospective analysis on 42 surgical specimens from idiopathic stenosis female patients (mean age, 52.4; age range, 31-79) and 28 gender- and age-matched controls. Methods: Immunoreactivity of ER-α, ER-β, and PR was calculated as the product of intensity (1 = weak, 2 = moderate, 3 = strong) and positive cell percentage (1-4, for < 10/10-50/50-80/ > 80%). This score was calculated on the stenotic and peristenotic tissues. Influence of menopausal status on hormonal expression and stenotic grade was tested. Results: Stenosis showed ER-α overexpression versus peristenotic tissue and controls (score 6.6 ± 4.4, 0.3 ± 0.5, and 2.2 ± 1.5, respectively; P < 0.001). Overexpression was even more marked for progesterone receptors (score 8.3 ± 3.6, 0.8 ± 0.6, and 1.0 ± 0.7, respectively; P < 0.001). There was no expression of ER-β in stenosis (score 0), whereas it was normally expressed in peristenotic tissue and controls (score 0.7 ± 0.5 and 0.5 ± 0.5; P < 0.001 vs. stenosis). Expression of ER-α was higher in postmenopausal stenotic patients (P < 0.01). This subgroup included a higher proportion of Cotton-Myer grade III stenosis than in premenopausal subjects (P < 0.001). Conclusion: An imbalance between ER-α, ER-β, and PR is present in idiopathic stenosis patients. The hormonal background may be involved in inappropriate inflammation and increased stenosis susceptibility. Menopausal changes seem to play a role in both stenosis grade and receptor patterns.