Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan; Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, PR China.
Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan; Department of Clinical Genomics, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
Hum Pathol. 2018 Nov;81:89-95. doi: 10.1016/j.humpath.2018.06.013. Epub 2018 Jun 23.
In the female genital tract, extrauterine leiomyomas such as those that arise in the ovary and paraovarian/paratubal regions are rare. Currently, little is known about the background genetic changes in such adnexal leiomyomas. Recent studies have found that the MED12 mutation is common in uterine leiomyomas, which suggests that such mutations may play an oncogenic role in smooth muscle neoplasms in females. Herein, we examined a series of ovarian and other adnexal leiomyomas in terms of MED12 mutational status to investigate possible MED12 involvement in the pathogenesis of extrauterine smooth muscle tumors. We evaluated 10 cases of adnexal leiomyomas (5 ovarian, 3 paraovarian, and 2 paratubal) and 49 cases of ovarian sex cord-stromal tumors as controls. We performed polymerase chain reaction followed by direct sequencing of exon 2 of MED12, and immunohistochemical staining for smooth muscle actin and desmin. We identified somatic MED12 mutations in 90% (9/10) of the adnexal leiomyomas. None of the sex cord-stromal tumors in the control group harbored MED12 mutations. Diffuse immunoreactivity for both smooth muscle actin and desmin was characteristic of adnexal leiomyomas only. Thus, we conclude that ovarian leiomyomas are distinct from sex cord-stromal tumors. MED12 mutations are key molecular features of ovarian and other adnexal leiomyomas. We speculate that the pathogenesis of adnexal leiomyoma is similar to that of its uterine counterpart.
在女性生殖器官中，卵巢和附件（卵巢旁/输卵管旁）部位的子宫外平滑肌瘤等非常罕见。目前，对于这些附件平滑肌瘤的遗传背景改变知之甚少。最近的研究发现，MED12 突变在子宫平滑肌瘤中很常见，这表明这种突变可能在女性平滑肌肿瘤中发挥致癌作用。在此，我们研究了一系列卵巢和其他附件平滑肌瘤的 MED12 突变状态，以探讨 MED12 是否可能参与了子宫外平滑肌肿瘤的发病机制。我们评估了 10 例附件平滑肌瘤（5 例卵巢、3 例卵巢旁、2 例输卵管旁）和 49 例卵巢性索-间质肿瘤作为对照。我们对 MED12 外显子 2 进行聚合酶链反应（PCR）后直接测序，并对平滑肌肌动蛋白和结蛋白进行免疫组织化学染色。我们发现 90%（9/10）的附件平滑肌瘤存在体细胞 MED12 突变。对照组的性索-间质肿瘤均未发现 MED12 突变。附件平滑肌瘤仅表现为平滑肌肌动蛋白和结蛋白的弥漫性免疫反应。因此，我们得出结论，卵巢平滑肌瘤与性索-间质肿瘤不同。MED12 突变是卵巢和其他附件平滑肌瘤的关键分子特征。我们推测附件平滑肌瘤的发病机制与子宫平滑肌瘤相似。
