Abstract 1538: Molecular characterization of uterine leiomyomas, histopathological uterine leiomyoma subtypes, and uterine leiomyosarcomas

Abstract Uterine leiomyomas (ULMs) are the most common tumors of the female genital tract. They originate from the smooth muscle cells of the myometrium. Despite their benign nature, ULMs can cause considerable morbidity, such as excessive bleeding, abdominal pain, and infertility. They are also the most common cause for hysterectomy. Based on histopathology, ULMs can be divided into common leiomyomas and various subtypes, such as cellular, atypical, and mitotically active leiomyomas, that mimic malignancy in one or more aspects. Histopatological ULM subtypes are responsible for approximately 5% of all ULMs. In light of the current literature, ULMs may rarely undergo malignant transformation and develop into a leiomyosarcoma. We have previously reported that mediator complex subunit 12 (MED12) exon 2 is mutated in approximately 70% of ULMs. Our subsequent studies have indicated that both histopathological ULM subtypes (17.5%) and uterine leiomyosarcomas (7%) harbor MED12 exon 2 mutations significantly less frequently than common leiomyomas. The aim of this study is to examine the frequency of other known aberrations in ULMs, such as overexpression of HMGA1 and HMGA2, in histopathological ULM subtypes and uterine leiomyosarcomas. The study material consists of 213 formalin-fixed paraffin-embedded samples including 60 common leiomyomas, 93 histopathological ULM subtypes (cellular, atypical, and mitotically active leiomyomas), and 60 uterine leiomyosarcomas. We have constructed tissue microarrays of these distinct tumor groups for immunohistochemical stainings. In addition to HMGA1 and HMGA2 antibodies, various immunohistochemical markers, commonly used in gynecological pathology, will be utilized to analyze similarities and differences between the tumor groups. It is clinically relevant to identify tumor subtypes with different molecular genetic characteristics which might then lead to improved diagnosis, personalized medical treatments, and prognosis in the future. New knowledge of the mechanisms underlying the potential progression to malignancy is also essential, because, for example in the case of uterine leiomyosarcomas, diagnosis is often accidental and postoperative. Citation Format: Netta Mäkinen, Kati Kämpjärvi, Ralf Bützow, Pia Vahteristo. Molecular characterization of uterine leiomyomas, histopathological uterine leiomyoma subtypes, and uterine leiomyosarcomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1538. doi:10.1158/1538-7445.AM2014-1538