title: POLD2 and KSP37 (FGFBP2) correlate strongly with histology, stage and outcome in ovarian carcinomas.
abstract: BACKGROUND
  Epithelial ovarian cancer (EOC) constitutes more than 90% of ovarian cancers and is associated with high mortality. EOC comprises a heterogeneous group of tumours, and the causes and molecular pathology are essentially unknown. Improved insight into the molecular characteristics of the different subgroups of EOC is urgently needed, and should eventually lead to earlier diagnosis as well as more individualized and effective treatments. Previously, we reported a limited number of mRNAs strongly upregulated in human osteosarcomas and other malignancies, and six were selected to be tested for a possible association with three subgroups of ovarian carcinomas and clinical parameters.
  
  
  RESULTS
  The six selected mRNAs were quantified by RT-qPCR in biopsies from eleven poorly differentiated serous carcinomas (PDSC, stage III-IV), twelve moderately differentiated serous carcinomas (MDSC, stage III-IV) and eight clear cell carcinomas (CCC, stage I-IV) of the ovary. Superficial scrapings from six normal ovaries (SNO), as well as biopsies from three normal ovaries (BNO) and three benign ovarian cysts (BBOC) were analyzed for comparison. The gene expression level was related to the histological and clinical parameters of human ovarian carcinoma samples. One of the mRNAs, DNA polymerase delta 2 small subunit (POLD2), was increased in average 2.5- to almost 20-fold in MDSC and PDSC, respectively, paralleling the degree of dedifferentiation and concordant with a poor prognosis. Except for POLD2, the serous carcinomas showed a similar transcription profile, being clearly different from CCC. Another mRNA, Killer-specific secretory protein of 37 kDa (KSP37) showed six- to eight-fold higher levels in CCC stage I compared with the more advanced staged carcinomas, and correlated positively with an improved clinical outcome.
  
  
  CONCLUSIONS
  We have identified two biomarkers which are markedly upregulated in two subgroups of ovarian carcinomas and are also associated with stage and outcome. The results suggest that POLD2 and KSP37 might be potential prognostic biomarkers.
authors.affiliation: Department of Gynaecology, Oslo University Hospital, Oslo, Norway. bente.vilming.elgaaen@medisin.uio.no
authors.forename: Bente Vilming
authors.initials: BV
authors.lastname: Elgaaen
authors.forename: Kari Bente Foss
authors.initials: KB
authors.lastname: Haug
authors.forename: Junbai
authors.initials: J
authors.lastname: Wang
authors.forename: Ole Kristoffer
authors.initials: OK
authors.lastname: Olstad
authors.forename: Dario
authors.initials: D
authors.lastname: Fortunati
authors.forename: Mathias
authors.initials: M
authors.lastname: Onsrud
authors.forename: Anne Cathrine
authors.initials: AC
authors.lastname: Staff
authors.forename: Torill
authors.initials: T
authors.lastname: Sauer
authors.forename: Kaare M
authors.initials: KM
authors.lastname: Gautvik
mesh_terms: D000368:Aged; D001798:Blood Proteins / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis / Q000235:genetics; D004258:DNA Polymerase III / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000235:genetics; D017063:Outcome Assessment, Health Care; D010048:Ovarian Cysts / Q000175:diagnosis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001798:Blood Proteins; C431908:FGFBP2 protein, human; D012333:RNA, Messenger; D004258:DNA Polymerase III