title: Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.
abstract: BACKGROUND
  Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer.
  
  
  METHODS
  HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS).
  
  
  RESULTS
  Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade.
  
  
  CONCLUSIONS
  HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.
authors.affiliation: Dept of Obstetrics and Gynaecology, National Maternity Hospital, Holles Street, Dublin 2, Ireland. donal.brennan@ucd.ie
authors.forename: Donal J
authors.initials: DJ
authors.lastname: Brennan
authors.forename: Jenny
authors.initials: J
authors.lastname: Brändstedt
authors.forename: Elton
authors.initials: E
authors.lastname: Rexhepaj
authors.forename: Michael
authors.initials: M
authors.lastname: Foley
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.forename: William M
authors.initials: WM
authors.lastname: Gallagher
authors.forename: Darran P
authors.initials: DP
authors.lastname: O'Connor
authors.forename: Colm
authors.initials: C
authors.lastname: O'Herlihy
authors.forename: Karin
authors.initials: K
authors.lastname: Jirstrom
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis*; D007150:Immunohistochemistry; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology* / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D006903:Hydroxymethylglutaryl CoA Reductases