title: Prognostic value of human epididymis protein 4 in endometrial cancer and its utility for surgical staging.
abstract: OBJECTIVE
  An optimal surgical staging in the group of patients with the high-risk type of endometrial cancer is often limited by age and serious internal comorbidities. Therefore, in this study we focused on human epididymis protein 4 and its contribution to the preoperative differentiation of prognostically distinct groups of patients and to individualized surgical treatment as compared with cancer antigen (CA) 125 and imaging methods.
  
  
  METHODS
  The study included 115 patients with endometrioid adenocarcinoma diagnosed through endometrial biopsy. Before the final operation, blood sampling was performed for the determination of human epididymis protein 4 (HE4) and CA125 levels. Serum levels of both biomarkers were analyzed in relation to individual prognostic factors (stage of disease, depth of myometrial invasion, tumor grade, risk type of disease).
  
  
  RESULTS
  In the case of HE4, we demonstrated a statistically significant difference (P < 0.001) between patients with low and high risk of the disease. In our model, achieving the maximum sum of sensitivity and specificity, HE4 shows a sensitivity of 72.4% and a specificity of 75.4% for the cut-off 76.5 pmol/L and is a better predictor in distinguishing the high-risk patients than CA125 (area under the curve 0.77 for HE vs 0.71 for CA125).
  
  
  CONCLUSIONS
  HE4 is a marker that could complement the findings of imaging techniques and that may be useful in decision-making on how to individualize surgical staging. The possibility of its introduction as an independent marker in routine practice remains, at the moment however, limited. The optimal cut-off for HE4 has not been established yet and further studies are needed.
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, Masaryk University Brno and Faculty Hospital Brno, Brno, Czech Republic.
authors.forename: Lubos
authors.initials: L
authors.lastname: Minar
authors.affiliation: Department of Biochemistry, Faculty Hospital Brno, Brno, Czech Republic.
authors.forename: Ivanka
authors.initials: I
authors.lastname: Klabenesova
authors.affiliation: Department of Pathology, Faculty Hospital Brno, Brno, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Jandakova
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Zlamal
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic.
authors.forename: Julie
authors.initials: J
authors.lastname: Bienertova-Vasku
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D018269:Carcinoma, Endometrioid / Q000097:blood* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000097:blood* / Q000473:pathology; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood; D009215:Myometrium / Q000473:pathology; D009367:Neoplasm Staging; D011506:Proteins / Q000378:metabolism*; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: endometrial cancer; human epididymis protein 4; risk status of disease; surgical staging