HMG-CoA reductase expression in breast cancer is associated with a less aggressive phenotype and influenced by anthropometric factors.
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.
Department of Laboratory Medicine, Center for Molecular Pathology, Malmö University Hospital, Malmö, Sweden.
Signe
S
Borgquist
Soraya
S
Djerbi
Fredrik
F
Pontén
Lola
L
Anagnostaki
Malin
M
Goldman
Alexander
A
Gaber
Jonas
J
Manjer
Göran
G
Landberg
Karin
K
Jirström
D050153:Abdominal Fat; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D015914:Estrogen Replacement Therapy; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis*; D007150:Immunohistochemistry; D015994:Incidence; D008875:Middle Aged; D010641:Phenotype; D016016:Proportional Hazards Models; D012307:Risk Factors; D049629:Waist-Hip Ratio
D014408:Biomarkers, Tumor; D006903:Hydroxymethylglutaryl CoA Reductases