MED12 is frequently mutated in ovarian and other adnexal leiomyomas.

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.