title: Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients.
abstract: BACKGROUND
  To date, no good marker for screening or disease monitoring of endometrial cancer (EC) is available. The aims of this study were to investigate HE4 gene, protein expression and serum HE4 (sHE4) levels in a panel of ECs and normal endometria (NEs) and to correlate sHE4 with patient clinicopathological characteristics and prognosis.
  
  
  METHODS
  Using quantitative real-time PCR we tested 46 ECs and 20 NEs for HE4 gene expression. Protein expression was analysed by immunohistochemistry on tissue microarrays in 153 ECs and 33 NEs. Pre-operative serum samples from 138 EC and 76 NE patients were analysed with HE4-EIA assay. Association between sHE4 and patient clinicopathological characteristics or outcome was evaluated.
  
  
  RESULTS
  Protein and HE4 gene were significantly upregulated in EC tissues and sera, compared with controls. High sHE4 levels were significantly associated with worse EC clinical characteristics. By univariate survival analysis, high sHE4 levels significantly correlated with decreased overall survival, progression-free survival and disease-free survival, retaining their independent prognostic value on the poorly differentiated EC cohort.
  
  
  CONCLUSIONS
  We demonstrate, for the first time, that high sHE4 levels correlates with an aggressive EC phenotype and may constitute an independent prognostic factor for poorly differentiated-ECs. Determination of sHE4 could be clinically useful in identifying high-risk EC patients for a more aggressive adjuvant therapy.
authors.affiliation: Angelo Nocivelli Institute of Molecular Medicine, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. bignottieliana@yahoo.it
authors.forename: E
authors.initials: E
authors.lastname: Bignotti
authors.forename: M
authors.initials: M
authors.lastname: Ragnoli
authors.forename: L
authors.initials: L
authors.lastname: Zanotti
authors.forename: S
authors.initials: S
authors.lastname: Calza
authors.forename: M
authors.initials: M
authors.lastname: Falchetti
authors.forename: S
authors.initials: S
authors.lastname: Lonardi
authors.forename: S
authors.initials: S
authors.lastname: Bergamelli
authors.forename: E
authors.initials: E
authors.lastname: Bandiera
authors.forename: R A
authors.initials: RA
authors.lastname: Tassi
authors.forename: C
authors.initials: C
authors.lastname: Romani
authors.forename: P
authors.initials: P
authors.lastname: Todeschini
authors.forename: F E
authors.initials: FE
authors.lastname: Odicino
authors.forename: F
authors.initials: F
authors.lastname: Facchetti
authors.forename: S
authors.initials: S
authors.lastname: Pecorelli
authors.forename: A
authors.initials: A
authors.lastname: Ravaggi
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D018394:CA-125 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D004717:Endometrium / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D030501:Epididymal Secretory Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D057234:Preoperative Period; D011379:Prognosis; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000378:metabolism; D023083:beta-Defensins
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C426184:DEFB126 protein, human; D030501:Epididymal Secretory Proteins; D012333:RNA, Messenger; D023083:beta-Defensins