Ivana Fiz1, Wiebke Antonopoulos2, Jan-Constantin Kölmel3, Karina Rüller4, Francesco Fiz5,6, Cesare Piazza7,8, Giorgio Peretti9,10, Christa Flechtenmacher2, Peter Schirmacher2, Christian Sittel3. 1. Department of Otorhinolaryngology, IRCCS Instituto Giannina Gaslini, Genoa, Italy. 2. Institute of Pathology, University Hospital, Heidelberg, Germany. 3. Department of Otorhinolaryngology-Head and Neck Surgery, Klinikum Stuttgart, Stuttgart, Germany. 4. Department of Otorhinolaryngology-Head and Neck Surgery, Klinikum Stuttgart, Stuttgart, Germany. karinarueller@gmail.com. 5. Nuclear Medicine Unit, Department of Radiology, University of Tübingen, Tübingen, Germany. 6. Nuclear Medicine Unit, E.O. Ospedali Galliera, Genoa, Italy. 7. Department of Otorhinolaryngology-Head and Neck Surgery, ASST Spedali Civili of Brescia, Brescia, Italy. 8. Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy. 9. Department of Otorhinolaryngology-Head and Neck Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 10. Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.
Abstract
PURPOSE: Our previous study on the idiopathic progressive subglottic stenosis (IPSS) highlighted a possible hormonal mechanism, with over-expression of estrogen receptors alpha (ER-α) and progesterone receptors (PR). We tested whether such over-expression take place in non-idiopathic subglottic stenosis (NISS) as well. METHODS: 37 specimens of iatrogenic NISS were analyzed (20 females; mean age, 59 ± 12 years; range 41-85). Immunoreactivity of ER-α and PR was calculated as the product of intensity (1 = weak, 2 = moderate, 3 = strong) and positive cells percentage (1 to 4, for < 10%, 10-50%, 50-80%, and > 80%). This score was calculated on the stenotic tissue (ST), and stenosis margins (SM). RESULTS: The expression of PR was significantly higher in ST of IPSS compared with female and male NISS patients (8.7 ± 3.1 vs. 4.9 ± 3.2, p < 0.001 for IPSS vs. female and 8.7 ± 3.1 vs. 2.1 ± 2.7, p < 0.01 for IPSS vs. male NISS patients). Contrarily, ER-α showed gender differences, as both IPSS and female NISS patients had similar, yet higher ER-α expression compared with male NISS patients (7.0 ± 4.2 vs. 6.5 ± 2.5, p = NS for IPSS vs. female and 7.0 ± 4.2 vs. 3.4 ± 2.0, p < 0.02 for IPSS vs. male NISS patients). There was no difference in fibroblast receptor expression between ST and SM. However, ER-α and PR expression was significantly lower in marginal mucous glands when compared with ST. CONCLUSIONS: The IPSS pathogenesis appears to be driven by hormonal mechanisms, in particular, by over-expression of PR. Marginal cells display a reduced hormone receptor density. This finding could be interpreted as a compensatory mechanism. These findings could open up for targeted IPSS treatment.
PURPOSE: Our previous study on the idiopathic progressive subglottic stenosis (IPSS) highlighted a possible hormonal mechanism, with over-expression of estrogen receptors alpha (ER-α) and progesterone receptors (PR). We tested whether such over-expression take place in non-idiopathic subglottic stenosis (NISS) as well. METHODS: 37 specimens of iatrogenic NISS were analyzed (20 females; mean age, 59 ± 12 years; range 41-85). Immunoreactivity of ER-α and PR was calculated as the product of intensity (1 = weak, 2 = moderate, 3 = strong) and positive cells percentage (1 to 4, for < 10%, 10-50%, 50-80%, and > 80%). This score was calculated on the stenotic tissue (ST), and stenosis margins (SM). RESULTS: The expression of PR was significantly higher in ST of IPSS compared with female and male NISS patients (8.7 ± 3.1 vs. 4.9 ± 3.2, p < 0.001 for IPSS vs. female and 8.7 ± 3.1 vs. 2.1 ± 2.7, p < 0.01 for IPSS vs. male NISS patients). Contrarily, ER-α showed gender differences, as both IPSS and female NISS patients had similar, yet higher ER-α expression compared with male NISS patients (7.0 ± 4.2 vs. 6.5 ± 2.5, p = NS for IPSS vs. female and 7.0 ± 4.2 vs. 3.4 ± 2.0, p < 0.02 for IPSS vs. male NISS patients). There was no difference in fibroblast receptor expression between ST and SM. However, ER-α and PR expression was significantly lower in marginal mucous glands when compared with ST. CONCLUSIONS: The IPSS pathogenesis appears to be driven by hormonal mechanisms, in particular, by over-expression of PR. Marginal cells display a reduced hormone receptor density. This finding could be interpreted as a compensatory mechanism. These findings could open up for targeted IPSS treatment.
Authors: Alexander Gelbard; David O Francis; Vlad C Sandulache; John C Simmons; Donald T Donovan; Julina Ongkasuwan Journal: Laryngoscope Date: 2014-10-07 Impact factor: 3.325