Department of Gynecology, University Hospital Zurich and University of Zurich, Switzerland.
Department of Gynecology and Obstetrics, Kantonsspital Schaffhausen, Switzerland.
Eur J Obstet Gynecol Reprod Biol. 2024 Nov;302:73-80. doi: 10.1016/j.ejogrb.2024.08.044. Epub 2024 Aug 31.
Endometriosis is a disease affecting approximately 10% of reproductive age women. Loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A) occurs in some endometriosis cases. Histone deacetylase 6 (HDAC-6) is an enzyme with implication in several diseases including different cancer types and immunological disorders, where it is involved in protein trafficking and degradation, cell shape, and migration. In ARID1A-deficient ovarian cancer increased HDAC-6 expression lead to apoptosis-inhibiting post-translational modification of p53. It is not known if HDAC-6 expression is also altered in ARID1A-deficient endometriosis. The aim of this study was to assess HDAC-6 expression in endometriotic lesions in correlation to ARID1A-status. Two tissue-microarrays with 168 endometriotic lesions, including ovarian (64/168, 38 %), peritoneal (66/168, 39 %) and deep-infiltrating (38/168, 23 %) subtypes, and 73 endometrium of women without endometriosis were assessed. Mean ARID1A immunoreactivity score (IRS) in endometriosis group was 10.83 (±2.36) and 10.78 (±1.94) in the epithelium and stroma, respectively, while the respective mean HDAC6 IRS were 9.16 (±2.76) and 5.94 (±2.88). The comparison of the HDAC6 expression between endometriosis subtypes showed higher expression in deep-infiltrating endometriosis, in both, epithelium (p = 0.032) and stroma (p = 0.007). In ARID1A negative cases, epithelial expression of HDAC6 was higher in endometriosis compared to women without endometriosis (p = 0.031), and this was also specifically observed in the subset of ovarian endometriosis (p = 0.037). There were no significant differences in the stromal expression of HDAC6. In conclusion, our results demonstrate a complex expression pattern of HDAC6 depending on ARID1A status in different endometriosis subtypes. Further studies on HDAC6 and ARID1A are important to elucidate mechanisms involved in malignant transformation of endometriosis.
子宫内膜异位症是一种影响大约 10%育龄妇女的疾病。在一些子宫内膜异位症病例中，肿瘤抑制基因富含 AT 相互作用结构域蛋白 1A（ARID1A）丢失。组蛋白去乙酰化酶 6（HDAC-6）是一种在包括不同癌症类型和免疫性疾病在内的多种疾病中具有潜在作用的酶，它参与蛋白质运输和降解、细胞形态和迁移。在 ARID1A 缺陷型卵巢癌中，HDAC-6 表达增加导致 p53 的翻译后抑制凋亡修饰。目前尚不清楚 ARID1A 缺陷型子宫内膜异位症中 HDAC-6 的表达是否也发生改变。本研究旨在评估 ARID1A 状态与子宫内膜异位症病变中 HDAC-6 表达的相关性。两个组织微阵列包含 168 个子宫内膜异位症病变，包括卵巢（64/168，38%）、腹膜（66/168，39%）和深部浸润（38/168，23%）亚型，以及 73 名无子宫内膜异位症的女性子宫内膜。子宫内膜异位症组 ARID1A 免疫反应评分（IRS）平均值为 10.83（±2.36）和 10.78（±1.94），上皮和基质分别为 9.16（±2.76）和 5.94（±2.88）。比较子宫内膜异位症亚型的 HDAC6 表达，发现深部浸润性子宫内膜异位症中 HDAC6 的表达更高，上皮（p=0.032）和基质（p=0.007）均如此。在 ARID1A 阴性病例中，与无子宫内膜异位症的女性相比，子宫内膜异位症中 HDAC6 的上皮表达更高（p=0.031），在卵巢子宫内膜异位症亚组中也观察到这种情况（p=0.037）。HDAC6 基质表达无显著差异。总之，我们的结果表明，不同子宫内膜异位症亚型中 HDAC6 的表达模式复杂，取决于 ARID1A 状态。进一步研究 HDAC6 和 ARID1A 对于阐明子宫内膜异位症恶性转化的机制非常重要。
