Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium; Anatomopathology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Reprod Biomed Online. 2023 Sep;47(3):103248. doi: 10.1016/j.rbmo.2023.06.003. Epub 2023 Jun 15.
How are markers of cell death, invasiveness and progesterone signalling expressed in endometrium and ectopic lesions from adenomyosis patients?
Formalin-fixed paraffin-embedded tissue was collected from 15 control and 15 adenomyosis participants . To assess cell survival capacity, caspase 3 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) were immunolabelled as markers of apoptosis and autophagy respectively. Matrix metalloproteinase 9 (MMP9) expression served as a marker of extracellular matrix degradation and invasion activity. Progesterone receptors were immunostained to detect evidence of progesterone resistance.
Caspase 3 expression was significantly lower in the stromal (P = 0.0013) and epithelial (P = 0.0157) compartments of adenomyotic lesions than in healthy endometrial tissue. In the stroma, caspase 3 expression was significantly weaker in lesions than in corresponding eutopic endometrium (P = 0.0006). LC3B immunostaining was significantly decreased in adenomyotic stroma compared with corresponding eutopic endometrium (P = 0.0349). A significantly higher expression of MMP9 was detected in eutopic stroma from adenomyosis patients than in healthy tissue (P = 0.0295). Progesterone receptor immunostaining was found to be significantly weaker in the stroma of endometrium and ectopic lesions from adenomyosis patients than disease-free women (P = 0.0001; P = 0.0021).
Adenomyotic lesions show lower levels of apoptosis and autophagy, suggesting that aberrant cell survival may be involved in disease pathogenesis. MMP9 appears to contribute to endometrial invasiveness in adenomyosis, as its expression is more pronounced in endometrium from these women than women without the disease. Evidence of progesterone resistance can be found in endometrium and ectopic lesions from adenomyosis patients, and may drive disease development and account for the failure of certain patients to respond to progestogens.
在子宫内膜异位症患者的子宫内膜和异位病灶中，细胞死亡、侵袭和孕激素信号的标志物如何表达？
从 15 名对照和 15 名腺肌病患者中收集福尔马林固定石蜡包埋的组织。为了评估细胞存活能力，用半胱天冬酶 3 和微管相关蛋白 1A/1B 轻链 3B（LC3B）作为细胞凋亡和自噬的标志物进行免疫标记。基质金属蛋白酶 9（MMP9）的表达作为细胞外基质降解和侵袭活性的标志物。孕激素受体的免疫染色用于检测孕激素抵抗的证据。
与健康子宫内膜组织相比，腺肌病病灶的间质（P=0.0013）和上皮（P=0.0157）区的半胱天冬酶 3 表达明显降低。在间质中，病灶中的半胱天冬酶 3 表达明显弱于相应的在位子宫内膜（P=0.0006）。与相应的在位子宫内膜相比，腺肌病间质中的 LC3B 免疫染色明显减少（P=0.0349）。在腺肌病患者的在位子宫内膜中检测到 MMP9 的表达明显高于健康组织（P=0.0295）。与无疾病的女性相比，腺肌病患者的子宫内膜和异位病灶的基质中孕激素受体免疫染色明显较弱（P=0.0001；P=0.0021）。
腺肌病病灶显示出较低水平的细胞凋亡和自噬，这表明异常的细胞存活可能参与疾病的发病机制。MMP9 可能有助于子宫内膜在腺肌病中的侵袭，因为其在这些女性的子宫内膜中的表达比无疾病的女性更为明显。在腺肌病患者的子宫内膜和异位病灶中可以发现孕激素抵抗的证据，并且可能导致疾病的发展，并解释为什么某些患者对孕激素没有反应。
