Research article
Prognostic impact of tumour-specific HMG-CoA reductase expression in primary breast cancer
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* Corresponding author: Karin Jirström karin.jirstrom@med.lu.se
1 Center for Molecular Pathology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, SE-205 02 Malmö, Sweden
2 Division of Oncology, Department of Clinical Sciences, Lund University Hospital, SE-221 85 Lund, Sweden
3 CREATE Health Center for Translational Cancer Research, Lund University, SE-221 84 Lund, Sweden
4 Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, SE-751 85 Sweden
5 Division of Surgery, Department of Clinical Sciences, Lund University Hospital, SE-221 85 Lund, Sweden
6 UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
Breast Cancer Research 2008, 10:R79 doi:10.1186/bcr2146
Published: 22 September 2008Abstract
Introduction
We have previously reported that tumour-specific expression of the rate-limiting enzyme, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR), in the mevalonate pathway is associated with more favourable tumour parameters in breast cancer. In the present study, we examined the prognostic value of HMG-CoAR expression in a large cohort of primary breast cancer patients with long-term follow up.
Methods
The expression of HMG-CoAR was assessed by immunohistochemistry on tissue microarrays with tumour specimens from 498 consecutive cases of breast cancer with a median follow-up of 128 months. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the rate of recurrence-free survival (RFS) and breast cancer specific survival (BCSS).
Results
In line with our previous findings, tumour-specific HMG-CoAR expression was associated with low grade (p < 0.001), small size (p = 0.007), oestrogen receptor (ER) positive (p = 0.01), low Ki-67 (p = 0.02) tumours. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS, even when adjusted for established prognostic factors (relative risk [RR] = 0.60, 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In ER-negative tumours, however, there was a trend, that was not significantly significant, towards a shorter RFS in HMG-CoAR expressing tumours.
Conclusions
HMG-CoAR expression is an independent predictor of a prolonged RFS in primary breast cancer. This may, however, not be true for ER-negative tumours. Further studies are needed to shed light on the value of HMG-CoAR expression as a surrogate marker of response to statin treatment, especially with respect to hormone receptor status.