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

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    Authors
    Brennan, Donal J
    Brändstedt, Jenny
    Rexhepaj, Elton
    Foley, Michael
    Pontén, Fredrik
    Uhlén, Mathias
    Gallagher, William M
    O'Connor, Darran P
    O'Herlihy, Colm
    Jirstrom, Karin
    Affiliation
    Dept of Obstetrics and Gynaecology, National Maternity Hospital, Holles Street, Dublin 2, Ireland. donal.brennan@ucd.ie
    Issue Date
    2010
    MeSH
    Disease-Free Survival
    Female
    Humans
    Hydroxymethylglutaryl CoA Reductases
    Immunohistochemistry
    Microarray Analysis
    Middle Aged
    Neoplasm Recurrence, Local
    Neoplasm Staging
    Ovarian Neoplasms
    Tumor Markers, Biological
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    Citation
    Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer. 2010, 10:125 BMC Cancer
    Journal
    BMC cancer
    URI
    http://hdl.handle.net/10147/106901
    DOI
    10.1186/1471-2407-10-125
    PubMed ID
    20359358
    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.
    Language
    en
    ISSN
    1471-2407
    ae974a485f413a2113503eed53cd6c53
    10.1186/1471-2407-10-125
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