Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

BMC Cancer. 2010 Apr 1;10:125. doi: 10.1186/1471-2407-10-125.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Disease-Free Survival
  • Female
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / biosynthesis*
  • Immunohistochemistry
  • Microarray Analysis / methods
  • Middle Aged
  • Neoplasm Recurrence, Local / enzymology*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Hydroxymethylglutaryl CoA Reductases