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

Hdl Handle:
http://hdl.handle.net/10147/132543
Title:
Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer
Authors:
Brennan, Donal J; Brandstedt, Jenny; Rexhepaj, Elton; Foley, Michael; Ponten, Fredrik; Uhlen, Mathias; Gallagher, William M; O'Connor, Darran P; O'Herlihy, Colm; Jirstrom, Karin
Citation:
BMC Cancer. 2010 Apr 01;10(1):125
Issue Date:
1-Apr-2010
URI:
http://hdl.handle.net/10147/132543
Abstract:
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.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorBrennan, Donal J-
dc.contributor.authorBrandstedt, Jenny-
dc.contributor.authorRexhepaj, Elton-
dc.contributor.authorFoley, Michael-
dc.contributor.authorPonten, Fredrik-
dc.contributor.authorUhlen, Mathias-
dc.contributor.authorGallagher, William M-
dc.contributor.authorO'Connor, Darran P-
dc.contributor.authorO'Herlihy, Colm-
dc.contributor.authorJirstrom, Karin-
dc.date.accessioned2011-06-03T13:59:33Z-
dc.date.available2011-06-03T13:59:33Z-
dc.date.issued2010-04-01-
dc.identifierhttp://dx.doi.org/10.1186/1471-2407-10-125-
dc.identifier.citationBMC Cancer. 2010 Apr 01;10(1):125-
dc.identifier.urihttp://hdl.handle.net/10147/132543-
dc.description.abstractAbstract 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.-
dc.titleTumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderBrennan et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2011-06-01T16:03:39Z-
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