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Open Access Highly Accessed Research article

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

Donal J Brennan12*, Jenny Brändstedt3, Elton Rexhepaj2, Michael Foley4, Fredrik Pontén5, Mathias Uhlén6, William M Gallagher2, Darran P O'Connor2, Colm O'Herlihy4 and Karin Jirstrom37

Author Affiliations

1 Dept of Obstetrics and Gynaecology, National Maternity Hospital, Holles Street, Dublin 2, Ireland

2 UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland

3 Center for Molecular Pathology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, Malmö, Sweden

4 UCD School of Medicine and Medical Science, National Maternity Hospital, Holles Street, Dublin 2, Ireland

5 Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

6 Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology, Stockholm, Sweden

7 CREATE Health Center for Translational Cancer Research, Lund University, Lund, Sweden

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BMC Cancer 2010, 10:125  doi:10.1186/1471-2407-10-125

Published: 1 April 2010

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.