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

Hdl Handle:
http://hdl.handle.net/10147/106901
Title:
Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.
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
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
Issue Date:
2010
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
MeSH:
Disease-Free Survival; Female; Humans; Hydroxymethylglutaryl CoA Reductases; Immunohistochemistry; Microarray Analysis; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Tumor Markers, Biological
ISSN:
1471-2407

Full metadata record

DC FieldValue Language
dc.contributor.authorBrennan, Donal Jen
dc.contributor.authorBrändstedt, Jennyen
dc.contributor.authorRexhepaj, Eltonen
dc.contributor.authorFoley, Michaelen
dc.contributor.authorPontén, Fredriken
dc.contributor.authorUhlén, Mathiasen
dc.contributor.authorGallagher, William Men
dc.contributor.authorO'Connor, Darran Pen
dc.contributor.authorO'Herlihy, Colmen
dc.contributor.authorJirstrom, Karinen
dc.date.accessioned2010-06-28T08:50:46Z-
dc.date.available2010-06-28T08:50:46Z-
dc.date.issued2010-
dc.identifier.citationTumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer. 2010, 10:125 BMC Canceren
dc.identifier.issn1471-2407-
dc.identifier.pmid20359358-
dc.identifier.doi10.1186/1471-2407-10-125-
dc.identifier.urihttp://hdl.handle.net/10147/106901-
dc.description.abstractBACKGROUND: 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.language.isoenen
dc.subject.meshDisease-Free Survival-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshHydroxymethylglutaryl CoA Reductases-
dc.subject.meshImmunohistochemistry-
dc.subject.meshMicroarray Analysis-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Recurrence, Local-
dc.subject.meshNeoplasm Staging-
dc.subject.meshOvarian Neoplasms-
dc.subject.meshTumor Markers, Biological-
dc.titleTumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.en
dc.contributor.departmentDept of Obstetrics and Gynaecology, National Maternity Hospital, Holles Street, Dublin 2, Ireland. donal.brennan@ucd.ieen
dc.identifier.journalBMC canceren

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