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PMID: 20359358 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

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

BMC cancer ·Vol. 10 ·2010-04-01 ·Pages 125

Brennan DJ, Brändstedt J, Rexhepaj E, Foley M, Pontén F, Uhlén M, Gallagher WM, O'Connor DP, O'Herlihy C, Jirstrom K

Abstract

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. 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). 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. 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.

MeSH Terms
Biomarkers, Tumor/biosynthesis Disease-Free Survival Female Humans Hydroxymethylglutaryl CoA Reductases/biosynthesis Immunohistochemistry Microarray Analysis/methods Middle Aged Neoplasm Recurrence, Local/enzymology,pathology Neoplasm Staging Ovarian Neoplasms/enzymology,pathology
Chemicals
Biomarkers, Tumor Hydroxymethylglutaryl CoA Reductases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Brennan Donal J
Dept of Obstetrics and Gynaecology, National Maternity Hospital, Holles Street, Dublin 2, Ireland. donal.brennan@ucd.ie
Brändstedt Jenny
Rexhepaj Elton
Foley Michael
Pontén Fredrik
Uhlén Mathias
Gallagher William M
O'Connor Darran P
O'Herlihy Colm
Jirstrom Karin
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Article Info
Journal
BMC cancer
Abbr.
BMC Cancer
ISSN
1471-2407
DOI
10.1186/1471-2407-10-125
Email
donal.brennan@ucd.ie
Published
2010-04-01
Epub
2010-00-01
Pages
125
Language
English
Region
England
NLM ID
100967800
PMCID
PMC3087316
Subset
IM
External Links
PubMed source DOI: 10.1186/1471-2407-10-125 PMC Full Text View journal details
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