HE4 is a novel tissue marker for therapy response and progestin resistance in medium- and low-risk endometrial hyperplasia

Abstract

Background: The aim of the present study was to investigate whether changes in the tissue expression of human epididymisspecific protein 4 (HE4) could predict therapy resistance and relapse after progestin hormone therapy for medium- and low-risk endometrial hyperplasia.<p> <p>Methods: Endometrial biopsies were obtained from women participating in a multicentre RCT performed according to the CONSORT guidelines; the women were randomly assigned to either LNG-IUS; 10 mg of oral medroxyprogesterone acetate (MPA) administered for 10 days per cycle; or 10 mg of oral MPA administered daily for 6 months. Of the 153 women who completed therapy, 141 had adequate material for immunohistochemistry in pre- and post-treatment biopsies. An antibody to HE4 (clone 12A2 monoclonal IgG1 antibody, Fujirebio Diagnostics, Inc.) was used for the immunohistochemical staining of the pre- and post-treatment biopsies from each participant. The expression of HE4 staining was evaluated by the histological score (H-score) using light microscopy.<p> <p>Results: Changes in the expression of HE4 (H-score) during therapy were related to the therapy group (Po0.001) and therapy response (Po0.001) of the individuals but could not predict relapse (P40.05). Changes in the intracellular bodies were shown to predict both the therapy response (P ¼ 0.038) and relapse (P ¼ 0.014).<p> <p>Conclusions: Changes in the expression of HE4 during progestin therapy regimens can predict therapy response or indicate progestin resistance for medium- and low-risk endometrial hyperplasia.