title: HE4 is a novel tissue marker for therapy response and progestin resistance in medium- and low-risk endometrial hyperplasia.
abstract: The aim of the present study was to investigate whether changes in the tissue expression of human epididymis-specific protein 4 (HE4) could predict therapy resistance and relapse after progestin hormone therapy for medium- and low-risk endometrial hyperplasia.
  
  
  
  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.
  
  
  
  Changes in the expression of HE4 (H-score) during therapy were related to the therapy group (P<0.001) and therapy response (P<0.001) of the individuals but could not predict relapse (P>0.05). Changes in the intracellular bodies were shown to predict both the therapy response (P=0.038) and relapse (P=0.014).
  
  
  
  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.
authors.affiliation: Department of Clinical Pathology, University Hospital of Tromsø, N-9038 Tromsø, Norway.|Research Group for Gynaecologic Oncology, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, N-9037 Tromsø, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Ørbo
authors.affiliation: Research Group for Gynaecologic Oncology, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, N-9037 Tromsø, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Arnes
authors.affiliation: Department of Clinical Pathology, University Hospital of Tromsø, N-9038 Tromsø, Norway.
authors.forename: Lena Myreng
authors.initials: LM
authors.lastname: Lyså
authors.affiliation: Department of Obstetrics and Gynecology, Skåne University Hospital, Lund, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Borgfeldt
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, N-9037 Tromsø, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Straume
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004714:Endometrial Hyperplasia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D002479:Inclusion Bodies / Q000648:ultrastructure; D016912:Levonorgestrel / Q000494:pharmacology / Q000627:therapeutic use*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D011230:Precancerous Conditions / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012306:Risk; D016896:Treatment Outcome; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D015415:Biomarkers; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human; D016912:Levonorgestrel; D017258:Medroxyprogesterone Acetate