Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer
2010 (English)In: BMC Cancer, ISSN 1471-2407, Vol. 10, 125- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2010. Vol. 10, 125- p.
REDUCTASE EXPRESSION, PERILLYL ALCOHOL, CELL-CYCLE, STATIN USE, FOLLOW-UP, RISK, MEVALONATE, INHIBITION, LOVASTATIN
Medical and Health Sciences Biological Sciences
IdentifiersURN: urn:nbn:se:kth:diva-28289DOI: 10.1186/1471-2407-10-125ISI: 000276817100001ScopusID: 2-s2.0-77950540366OAI: oai:DiVA.org:kth-28289DiVA: diva2:386987
FunderKnut and Alice Wallenberg Foundation
QC 201101132011-01-132011-01-122011-01-13Bibliographically approved