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非特发性和特发性进行性声门下狭窄的激素通路比较

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

作者信息

Fiz Ivana, Antonopoulos Wiebke, Kölmel Jan-Constantin, Rüller Karina, Fiz Francesco, Piazza Cesare, Peretti Giorgio, Flechtenmacher Christa, Schirmacher Peter, Sittel Christian

机构信息

Department of Otorhinolaryngology, IRCCS Instituto Giannina Gaslini, Genoa, Italy.

Institute of Pathology, University Hospital, Heidelberg, Germany.

出版信息

Eur Arch Otorhinolaryngol. 2023 Feb;280(2):775-780. doi: 10.1007/s00405-022-07615-0. Epub 2022 Aug 29.

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.

摘要

目的

我们之前关于特发性进行性声门下狭窄(IPSS)的研究强调了一种可能的激素机制,即雌激素受体α(ER-α)和孕激素受体(PR)的过度表达。我们测试了这种过度表达是否也发生在非特发性声门下狭窄(NISS)中。

方法

分析了37例医源性NISS标本(20例女性;平均年龄59±12岁;范围41 - 85岁)。ER-α和PR的免疫反应性计算为强度(1 =弱,2 =中度,3 =强)和阳性细胞百分比(1至4,分别对应<10%、10 - 50%、50 - 80%和>80%)的乘积。该评分在狭窄组织(ST)和狭窄边缘(SM)上计算。

结果

与女性和男性NISS患者相比,IPSS的ST中PR的表达显著更高(8.7±3.1 vs. 4.9±3.2,IPSS与女性相比p<0.001;8.7±3.1 vs. 2.1±2.7,IPSS与男性NISS患者相比p<0.01)。相反,ER-α显示出性别差异,因为IPSS和女性NISS患者的ER-α表达相似,但均高于男性NISS患者(7.0±4.2 vs. 6.5±2.5,IPSS与女性相比p =无显著性差异;7.0±4.2 vs. 3.4±2.0,IPSS与男性NISS患者相比p<0.02)。ST和SM之间的成纤维细胞受体表达没有差异。然而,与ST相比,边缘黏液腺中的ER-α和PR表达显著降低。

结论

IPSS的发病机制似乎由激素机制驱动,特别是PR的过度表达。边缘细胞显示出较低的激素受体密度。这一发现可被解释为一种代偿机制。这些发现可能为IPSS的靶向治疗开辟道路。

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