title: Wee1 is a novel independent prognostic marker of poor survival in post-chemotherapy ovarian carcinoma effusions.
abstract: OBJECTIVE
  Wee1-like kinase (Wee1) is a tyrosine kinase which negatively regulates entry into mitosis at the G2 to M-phase transition and has a role in inhibition of unscheduled DNA replication in S-phase. The present study investigated the clinical role of Wee1 in advanced-stage (FIGO III-IV) ovarian serous carcinoma.
  
  
  METHODS
  Wee1 protein expression was analyzed in 287 effusions using immunohistochemistry. Expression was analyzed for association with clinicopathologic parameters, including survival. Forty-five effusions were additionally studied using Western blotting. Wee1 was further silenced in SKOV3 and OVCAR8 cells by siRNA knockdown and proliferation was assessed.
  
  
  RESULTS
  Nuclear expression of Wee1 in tumor cells was observed in 265/287 (92%) and 45/45 (100%) effusions by immunohistochemistry and Western blotting, respectively. Wee1 expression by immunohistochemistry was significantly higher in post-chemotherapy disease recurrence compared to pre-chemotherapy effusions obtained at diagnosis (p=0.002). Wee1 silencing in SKOV3 and OVCAR8 cells reduced proliferation. In univariate survival analysis of the entire cohort, a trend was observed between high (>25% of cells) Wee1 expression and poor overall survival (p=0.083). Survival analysis for 109 patients with post-chemotherapy effusions showed significant association between Wee1 expression and poor overall survival (p=0.004), a finding which retained its independent prognostic role in Cox multivariate analysis (p=0.003).
  
  
  CONCLUSIONS
  Wee1 is frequently expressed in ovarian serous carcinoma effusions, and its expression is significantly higher following exposure to chemotherapy. The present study is the first to report that Wee1 is an independent prognostic marker in serous ovarian carcinoma.
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Ana
authors.initials: A
authors.lastname: Slipicevic
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Arild
authors.initials: A
authors.lastname: Holth
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Ellen
authors.initials: E
authors.lastname: Hellesylt
authors.affiliation: Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway; University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0316 Oslo, Norway.
authors.forename: Claes G
authors.initials: CG
authors.lastname: Tropé
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway; University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0316 Oslo, Norway. Electronic address: bend@medisin.uio.no.
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Vivi Ann
authors.initials: VA
authors.lastname: Flørenes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001202:Ascitic Fluid / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D016066:Pleural Effusion, Malignant / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human
keywords: Effusions; Ovarian carcinoma; Survival; Tumor progression; Wee1