Hormone pathway comparison in non-idiopathic and idiopathic progressive subglottic stenosis

Purpose Our previous study on the idiopathic progressive subglottic stenosis (IPSS) highlighted a possible hormonal mechanism, with over-expression of estrogen receptors alpha (ER-alpha) 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-alpha 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-alpha showed gender differences, as both IPSS and female NISS patients had similar, yet higher ER-alpha 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-alpha 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.