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HMG-CoA reductase expression in breast cancer is associated with a less aggressive phenotype and influenced by anthropometric factors.

Borgquist, Signe LU ; Djerbi, Soraya; Pontén, Fredrik; Anagnostaki, Lola; Goldman, Malin; Gaber, Alexander LU ; Manjer, Jonas LU ; Landberg, Göran LU and Jirström, Karin LU (2008) In International Journal of Cancer 123(5). p.1146-1153
Abstract
Although several studies have reported on the anti-tumoural properties exerted by 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) inhibitors (statins), the in vivo expression of HMG-CoAR in human cancer has been considerably less investigated. In our study, we examined the immunohistochemical expression of HMG-CoAR in 511 incident breast cancers within the Malmö Diet and Cancer Study in order to explore its relationship to established clinicopathological and tumour biological parameters. Furthermore, the potential influence of estrogen exposure on HMG-CoAR expression was assessed by performing Cox's proportional hazards analyses of the relationship between the use of hormone replacement therapy (HRT), obesity (waist... (More)
Although several studies have reported on the anti-tumoural properties exerted by 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) inhibitors (statins), the in vivo expression of HMG-CoAR in human cancer has been considerably less investigated. In our study, we examined the immunohistochemical expression of HMG-CoAR in 511 incident breast cancers within the Malmö Diet and Cancer Study in order to explore its relationship to established clinicopathological and tumour biological parameters. Furthermore, the potential influence of estrogen exposure on HMG-CoAR expression was assessed by performing Cox's proportional hazards analyses of the relationship between the use of hormone replacement therapy (HRT), obesity (waist circumference) and tumour-cell specific HMG-CoAR expression. We found that HMG-CoAR was present in various fractions and intensities in the cytoplasm, sometimes with a membranous pattern, but not in the tumour cell nuclei. The expression of HMG-CoAR was associated with a smaller tumour size (p = 0.02), low histological grade (p = 0.001), low Ki67 index (p = 0.004), ERalpha+ (p = 0.02), ERbeta+ (p = 0.005), and high p27 expression (p = <0.001). The incidence of tumours with a high HMG-CoAR-expression was increased among HRT-users, although this was not statistically significant in a heterogeneity analysis. Obesity was significantly associated with a high HMG-CoAR expression assessed both as a high (>50%) fraction of positive cells (relative risk: 2.06; 95% confidence interval: 1.20-3.51), and a strong staining intensity (2.33: 1.08-5.02). In summary, we demonstrate that HMG-CoAR is differentially expressed in breast cancer and that a high expression is associated with prognostically favourable tumour parameters. Moreover, estrogen related life-style and anthropometric factors might indeed regulate HMG-CoAR expression. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Cancer
volume
123
issue
5
pages
1146 - 1153
publisher
John Wiley & Sons
external identifiers
  • wos:000258243300021
  • pmid:18528862
  • scopus:47249094123
ISSN
0020-7136
DOI
10.1002/ijc.23597
language
English
LU publication?
yes
id
156a3ff9-ded3-4d39-b635-4528fa4d44a1 (old id 1169140)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18528862?dopt=Abstract
date added to LUP
2008-07-03 10:48:24
date last changed
2017-11-12 04:07:41
@article{156a3ff9-ded3-4d39-b635-4528fa4d44a1,
  abstract     = {Although several studies have reported on the anti-tumoural properties exerted by 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) inhibitors (statins), the in vivo expression of HMG-CoAR in human cancer has been considerably less investigated. In our study, we examined the immunohistochemical expression of HMG-CoAR in 511 incident breast cancers within the Malmö Diet and Cancer Study in order to explore its relationship to established clinicopathological and tumour biological parameters. Furthermore, the potential influence of estrogen exposure on HMG-CoAR expression was assessed by performing Cox's proportional hazards analyses of the relationship between the use of hormone replacement therapy (HRT), obesity (waist circumference) and tumour-cell specific HMG-CoAR expression. We found that HMG-CoAR was present in various fractions and intensities in the cytoplasm, sometimes with a membranous pattern, but not in the tumour cell nuclei. The expression of HMG-CoAR was associated with a smaller tumour size (p = 0.02), low histological grade (p = 0.001), low Ki67 index (p = 0.004), ERalpha+ (p = 0.02), ERbeta+ (p = 0.005), and high p27 expression (p = &lt;0.001). The incidence of tumours with a high HMG-CoAR-expression was increased among HRT-users, although this was not statistically significant in a heterogeneity analysis. Obesity was significantly associated with a high HMG-CoAR expression assessed both as a high (&gt;50%) fraction of positive cells (relative risk: 2.06; 95% confidence interval: 1.20-3.51), and a strong staining intensity (2.33: 1.08-5.02). In summary, we demonstrate that HMG-CoAR is differentially expressed in breast cancer and that a high expression is associated with prognostically favourable tumour parameters. Moreover, estrogen related life-style and anthropometric factors might indeed regulate HMG-CoAR expression.},
  author       = {Borgquist, Signe and Djerbi, Soraya and Pontén, Fredrik and Anagnostaki, Lola and Goldman, Malin and Gaber, Alexander and Manjer, Jonas and Landberg, Göran and Jirström, Karin},
  issn         = {0020-7136},
  language     = {eng},
  number       = {5},
  pages        = {1146--1153},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {HMG-CoA reductase expression in breast cancer is associated with a less aggressive phenotype and influenced by anthropometric factors.},
  url          = {http://dx.doi.org/10.1002/ijc.23597},
  volume       = {123},
  year         = {2008},
}