Ivana Fiz1, Zeid Bittar2, Cesare Piazza3, Jan Constantin Koelmel1, Federico Gatto4, Diego Ferone5, Francesco Fiz6, Diana Di Dio1, Alexander Bosse2, Giorgio Peretti5, Christian Sittel1. 1. Department of Otorhinolaryngology-Head and Neck Surgery, Katharinenhospital, Stuttgart, Germany. 2. Institute for Pathology, Katharinenhospital, Stuttgart, Germany. 3. Department of Otorhinolaryngology-Head and Neck Surgery, University of Brescia, Brescia, Italy. 4. Endocrinology Unit (DiMI), Department of Internal Medicine and Medical Specialties, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy. 5. Department of Otorhinolaryngology-Head and Neck Surgery, University of Genoa, Genoa, Italy. 6. Nuclear Medicine Unit, Department of Radiology, Uni-Klinikum Tuebingen, Tuebingen, Germany.
Abstract
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. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E72-E77, 2018.
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 stenoticpatients. 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 stenosispatients. 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. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E72-E77, 2018.