Abstract 120: Estrogen and progesterone receptor expression in different molecular uterine leiomyoma subclasses
Authors: Mäkinen Netta , Pasanen Annukka , Heinonen Hanna-Riikka , Kämpjärvi Kati , Bramante Simona , Mehine Miika , Jalkanen Jyrki , Heikinheimo Oskari , Sjöberg Jari , Bützow Ralf , Aaltonen Lauri 
Published: July 2016

Abstract
Uterine leiomyomas (ULs) are benign, estrogen- and progesterone-dependent smooth muscle tumors of the uterus. They are among the most common human neoplasms with an estimated prevalence of 20-40% in women of reproductive age, but also percentages as high as 77% have been reported. Although benign, ULs form a major burden to women's health. Approximately 25% of women with ULs have clinically relevant lesions, which cause morbidity and thus require treatment. As a consequence, ULs are the leading cause of hysterectomy worldwide. Despite the high prevalence and socio-economic impact of ULs, the molecular mechanisms underlying the growth and development of these lesions remain largely unknown. Familial, epidemiological, and cytogenetic studies indicate that genetic factors play a central role in the development of these lesions. Our recent findings, derived from the use of high-throughput technologies, have pointed to at least three distinct molecular UL subclasses, each candidate subclass displaying a characteristic genetic driver aberration as well as global gene expression profile: MED12 (mediator complex subunit 12) mutation-positive, HMGA2 (high mobility group AT-hook 2)-overexpressing, and FH (fumarate hydratase)-deficient ULs. Although the majority of ULs show estrogen and progesterone receptor (ER and PR) positivity on protein level, a subgroup of these tumors are ER- or PR-negative with an estimated frequency of up to 10%. The aim of this study is to assess the potential correlation between steroid receptor expression and different molecular UL subclasses. The study material consists of 1100 ULs collected from hysterectomy patients during surgery in Helsinki University Central Hospital and Central Finland Central Hospital, Finland. All ULs are systematically screened for MED12 mutations by Sanger sequencing. Because overexpression of HMGA2 typically arises through a chromosomal translocation, HMGA2-overexpressing ULs as well as FH-deficient tumors are tentatively identified using a high-density customizable Infinium® HumanCore-24+ BeadChip with 4000 additional custom markers that cover known genes, candidate regions, and single-nucleotide variations related to UL genesis. Also ULs without any known genetic driver aberrations are included in the study. ER and PR protein expression are analyzed by immunohistochemistry. Currently, molecular classification of the tumors plays no role in choosing treatment, but ULs are treated as a single entity. Different molecular subclasses may, however, use different molecular pathways, have different clinical outcome, or response to treatment. Identification of ER- and PR-negative ULs and their potential association with the genetic driver aberrations may provide important new information on the molecular mechanisms underlying UL genesis. Increased knowledge is also essential for developing new targeted treatments and improving management of the condition.
Citation Format: Netta Mäkinen, Annukka Pasanen, Hanna-Riikka Heinonen, Kati Kämpjärvi, Simona Bramante, Miika Mehine, Jyrki Jalkanen, Oskari Heikinheimo, Jari Sjöberg, Ralf Bützow, Lauri Aaltonen. Estrogen and progesterone receptor expression in different molecular uterine leiomyoma subclasses. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 120.