title: HE4 as a predictor of adjuvant chemotherapy resistance and survival in patients with epithelial ovarian cancer.
abstract: The aim of this study was to investigate the value of serum human epididymis protein 4 (HE4) and HE4 tissue protein expression to predict tumor resistance to adjuvant chemotherapy, progression-free survival (PFS), and overall survival in patients with epithelial ovarian cancer (EOC). Consecutive inclusion of 198 patients diagnosed with EOC was conducted. Blood samples were collected prior to surgery and tissue samples during surgery. Patient data were registered prospectively in the Danish Gynecologic Cancer Database. The association between serum HE4 and HE4 tissue protein expression, resistance to adjuvant chemotherapy, PFS, and overall survival were analyzed in univariate analyses and in multivariate analyses adjusted for age, performance score, surgical outcome, stage, grade, and histological subtype. Serum HE4 levels predicted chemotherapy resistance, PFS, and overall survival correlated significantly (p < 0.001) in the univariate analyses; but after adjustment in a multivariate model, serum HE4 was insignificant, except in a subgroup analysis of postmenopausal women, where serum HE4 significantly predicted resistance to chemotherapy and progression-free survival. HE4 tissue protein expression predicted PFS (p = 0.022) and overall survival (p = 0.047) in the univariate analysis, while HE4 tissue protein expression failed to predict these outcomes in the adjusted multivariate analyses. Serum HE4 or HE4 tissue protein expression are not independent factors of chemotherapy resistance or survival in patients with EOC, but serum HE4 might predict chemotherapy resistance and PFS in postmenopausal women.
authors.affiliation: Molecular Unit, Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.|Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mona
authors.initials: M
authors.lastname: Aarenstrup Karlsen
authors.affiliation: Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Høgdall
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Nedergaard
authors.affiliation: Molecular Unit, Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.|Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kira
authors.initials: K
authors.lastname: Philipsen Prahm
authors.affiliation: Molecular Unit, Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Nikoline Marie
authors.initials: NM
authors.lastname: Schou Karlsen
authors.affiliation: Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Weng Ekmann-Gade
authors.affiliation: Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tine
authors.initials: T
authors.lastname: Henrichsen Schnack
authors.affiliation: Molecular Unit, Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Tim
authors.initials: T
authors.lastname: Svenstrup Poulsen
authors.affiliation: Molecular Unit, Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Ib
authors.initials: I
authors.lastname: Jarle Christensen
authors.affiliation: Molecular Unit, Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Estrid
authors.initials: E
authors.lastname: Høgdall
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003718:Denmark; D018450:Disease Progression; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D010053:Ovary / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D011506:Proteins / Q000032:analysis*; D044967:Serum / Q000737:chemistry*; D016019:Survival Analysis; D016896:Treatment Outcome; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D000970:Antineoplastic Agents; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: HE4 tissue protein expression; Ovarian cancer; chemotherapy response; serum HE4; survival