title: Wilms tumor protein 1 (WT1)-- not only a diagnostic but also a prognostic marker in high-grade serous ovarian carcinoma.
abstract: OBJECTIVE
  Wilms tumor protein 1 (WT1) expression is used in gynecological pathology as a diagnostic marker of serous differentiation, and is frequently co-expressed with ER-α. Early phase studies on WT1 vaccine in gynecological cancers are ongoing. In this study we aimed to determine the prognostic value of WT1 in high-grade serous ovarian carcinoma.
  
  
  METHODS
  WT1 protein expression was determined by immunohistochemistry in a cohort of 207 primary high-grade serous ovarian carcinomas. WT1 mRNA expression was evaluated in a cohort of 1137 ovarian carcinomas from publically available gene expression datasets.
  
  
  RESULTS
  High WT1 expression was a significant positive prognostic factor in primary high-grade serous ovarian carcinoma regarding overall survival (OS, p=0.008) and progression free survival (PFS, p=0.015), which was independent of age, stage, and residual tumor (OS: p=0.024, PFS: p=0.047). The prognostic significance of immunohistochemical WT1 expression could be reproduced in an independent cohort of 72 patients. On the mRNA level the prognostic significance was validated in silico in publically available gene expression datasets including TCGA data (OS: p=0.002, PFS: p=0.011). WT1 expression was significantly linked to ER-α expression (p=0.001), and tumors that co-expressed both markers (WT1+/ER-α+) had a longer survival time than tumors of all other marker combinations (OS: p=0.002, PFS: p=0.013).
  
  
  CONCLUSIONS
  We present WT1 as a robust prognostic marker in high-grade serous ovarian carcinoma, which adds prognostic information to ER-α. This should be kept in mind when WT1 is used as a biomarker in the context of WT1-targeting therapies.
authors.affiliation: Institute of Pathology, Charité University Hospital, Berlin, Germany. Electronic address: eliane.taube@charite.de.
authors.forename: Eliane Tabea
authors.initials: ET
authors.lastname: Taube
authors.affiliation: Institute of Pathology, Charité University Hospital, Berlin, Germany; Tumor Bank Ovarian Cancer Network (TOC), Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.affiliation: Tumor Bank Ovarian Cancer Network (TOC), Berlin, Germany; Department of Gynecology, Charité University Hospital, Berlin, Germany.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Institute of Pathology, Charité University Hospital, Berlin, Germany.
authors.forename: Catarina Alisa
authors.initials: CA
authors.lastname: Kunze
authors.affiliation: Institute of Pathology, Charité University Hospital, Berlin, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.affiliation: Tumor Bank Ovarian Cancer Network (TOC), Berlin, Germany; Department of Gynecology, Charité University Hospital, Berlin, Germany.
authors.forename: Ioana
authors.initials: I
authors.lastname: Braicu
authors.affiliation: Department of Hematology and Oncology, Charité University Hospital, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Letsch
authors.affiliation: Institute of Pathology, Charité University Hospital, Berlin, Germany; Tumor Bank Ovarian Cancer Network (TOC), Berlin, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Darb-Esfahani
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D015203:Reproducibility of Results; D015996:Survival Rate; D025721:WT1 Proteins / Q000032:analysis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: ER-α; High-grade serous ovarian carcinoma; Prognostic marker; WT1