Niiro Emiko, Kawahara Naoki, Yamada Yuki, Yoshimoto Chiharu, Shimada Keiji, Sudo Tamotsu, Kobayashi Hiroshi
Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
Department of Diagnostic Pathology, Nara City Hospital, Nara, Japan.
J Obstet Gynaecol Res. 2019 Nov;45(11):2260-2266. doi: 10.1111/jog.14093. Epub 2019 Aug 14.
Expression of CD44 variant isoforms (CD44v) promotes the synthesis of reduced glutathione and contributes to reactive oxygen species defense through up-regulation of the intracellular antioxidant. The aim of the study was to investigate the expression of CD44v9 and oxidative DNA damage marker, 8-OHdG, in benign ovarian endometrioma (OE) and OE harboring clear cell carcinomas (CCC).
A retrospective study was performed at the Department of Gynecology, Nara Medical University hospital from January 2006 to December 2012. Patients with histologically confirmed benign OE (n = 27) and OE harboring areas of CCC (n = 8) were selected. Tissue samples were immunohistochemically analyzed for the presence of CD44v9 and 8-OHdG using avidin-biotin complex method.
CD44v9 was located on the cell membrane of endometriotic epithelial cells and expressed in 88.9% (24/27) of benign OE tissues. Only 25.0% (2/8) of benign endometriotic lesions adjacent to CCC was found to stain weakly for CD44v9. Percentage of CD44v9 positive cells was 68.5 ± 20.2% (mean ± standard deviation) of benign OE, 16.7 ± 16.5% of CCC endometriotic tissue (P < 0.001). Compared to benign OE, CCC endometriotic tissue showed a significant increase in the proportion of 8-OHdG expression (77.3 ± 22.5% vs 94.9 ± 3.0%, P = 0.049). A significant negative correlation was observed between CD44v9 status and 8-OHdG nuclear expression (r = -0.458, P = 0.006).
Alterations in CD44v9 and 8-OHdG may be associated with malignant transformation of benign OE.
CD44可变剪接异构体（CD44v）的表达可促进还原型谷胱甘肽的合成，并通过上调细胞内抗氧化剂来增强对活性氧的防御。本研究旨在调查CD44v9和氧化性DNA损伤标志物8-羟基脱氧鸟苷（8-OHdG）在良性卵巢子宫内膜异位囊肿（OE）及合并透明细胞癌（CCC）的OE中的表达情况。
于2006年1月至2012年12月在奈良医科大学医院妇科进行一项回顾性研究。选取经组织学确诊的良性OE患者（n = 27）及合并CCC区域的OE患者（n = 8）。采用抗生物素蛋白-生物素复合物法对组织样本进行免疫组织化学分析，以检测CD44v9和8-OHdG的存在情况。
CD44v9定位于子宫内膜异位上皮细胞的细胞膜，在88.9%（24/27）的良性OE组织中表达。在与CCC相邻的良性子宫内膜异位病变中，仅25.0%（2/8）对CD44v9呈弱阳性染色。CD44v9阳性细胞百分比在良性OE中为68.5±20.2%（平均值±标准差），在CCC子宫内膜异位组织中为16.7±16.5%（P < 0.001）。与良性OE相比，CCC子宫内膜异位组织中8-OHdG表达比例显著增加（77.3±22.5% vs 94.9±3.0%，P = 0.049）。观察到CD44v9状态与8-OHdG核表达之间存在显著负相关（r = -0.458，P = 0.006）。
CD44v9和8-OHdG的改变可能与良性OE的恶性转化有关。
