Kim Su Mi, Kim Yun Oh, Lee Min Kyoung, Chung Youn Jee, Jeung In Cheul, Kim Mee Ran, Kim Jang Heub
Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seocho, Seoul 06591, Republic of Korea.
Oncol Lett. 2019 Jan;17(1):532-538. doi: 10.3892/ol.2018.9565. Epub 2018 Oct 10.
Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) is a regulator of the female reproductive system, an indicator of ovarian reserve and a growth inhibitor of Müllerian duct-derived tumors and . The objective of the present study was to analyze MIS/AMH type II receptor (MIS/AMHRII) protein and mRNA expression in healthy human endometria compared with patients with endometrial hyperplasia and endometrial cancer, providing a foundation for MIS/AMH as a biological modifier for treatment of endometrial hyperplasia and endometrial cancer. The present study included healthy endometrial tissues (n=20), simple endometrial hyperplasia tissues without atypia (n=17), complex endometrial hyperplasia tissues without atypia (n=24) and endometrial cancer tissues (n=8). The location and variation of MIS/AMHRII protein expression was observed by immunohistochemistry. The expression was graded by two pathologists and was categorized as follows: Negative, weakly positive, moderately positive or strongly positive. Reverse transcription-quantitative polymerase chain reaction was used to quantify MIS/AMHRII mRNA expression. The expression of MIS/AMHRII protein was observed in the cytoplasm of healthy human endometria, endometrial hyperplasia and endometrial cancer cells. The frequency of MIS/AMHRII protein expression was 20.22±10.35% in the proliferative phase of the healthy endometrium and 24.09±11.73% in the secretory phase of the healthy endometrium. However, no differences were observed in the menstrual cycle phases. The frequency was 54.50±16.59% in endometrial hyperplasia without atypia, 55.10±15.87% in endometrial hyperplasia with atypia and 73.88±15.70% in endometrial cancer, indicating that expression was enhanced as the disease progressed from healthy to malignant status. In endometrial hyperplasia, MIS/AMHRII protein expression was significantly associated with histological complexity compared with atypia status. The present study demonstrated that MIS/AMHRII is present in healthy endometria, endometrial hyperplasia and endometrial cancer. The low expression frequency of MIS/AMHRII was not significantly different among normal endometrial tissues, however, the protein expression was elevated in endometrial hyperplasia and endometrial cancer. These findings indicated that the study of bioactive MIS/AMH, as a possible treatment for tumors expressing the MIS/AMH receptor, is essential.
苗勒管抑制物质/抗苗勒管激素(MIS/AMH)是女性生殖系统的一种调节因子,是卵巢储备的一个指标,也是苗勒管源性肿瘤的生长抑制剂。本研究的目的是分析健康人子宫内膜与子宫内膜增生和子宫内膜癌患者相比,MIS/AMH II型受体(MIS/AMHRII)蛋白和mRNA的表达情况,为将MIS/AMH作为治疗子宫内膜增生和子宫内膜癌的生物修饰剂提供依据。本研究纳入了健康子宫内膜组织(n = 20)、无异型性的单纯性子宫内膜增生组织(n = 17)、无异型性的复杂性子宫内膜增生组织(n = 24)和子宫内膜癌组织(n = 8)。通过免疫组织化学观察MIS/AMHRII蛋白表达的位置和变化。由两名病理学家对表达进行分级,并分类如下:阴性、弱阳性、中度阳性或强阳性。采用逆转录-定量聚合酶链反应来定量MIS/AMHRII mRNA的表达。在健康人子宫内膜、子宫内膜增生和子宫内膜癌细胞的细胞质中观察到MIS/AMHRII蛋白的表达。在健康子宫内膜的增殖期,MIS/AMHRII蛋白表达频率为20.22±10.35%,在健康子宫内膜的分泌期为24.09±11.73%。然而,在月经周期各阶段未观察到差异。在无异型性的子宫内膜增生中频率为54.50±16.59%,在有异型性的子宫内膜增生中为55.10±15.87%,在子宫内膜癌中为73.88±15.70%,表明随着疾病从健康状态发展到恶性状态,表达增强。在子宫内膜增生中,与异型性状态相比,MIS/AMHRII蛋白表达与组织学复杂性显著相关。本研究表明,MIS/AMHRII存在于健康子宫内膜、子宫内膜增生和子宫内膜癌中。在正常子宫内膜组织中,MIS/AMHRII的低表达频率无显著差异,然而,在子宫内膜增生和子宫内膜癌中蛋白表达升高。这些发现表明,研究生物活性MIS/AMH作为表达MIS/AMH受体肿瘤的一种可能治疗方法至关重要。