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1:
Cancer Res.
2007 Nov 1;67(21):10608-17. Epub 2007 Oct 29.
Related Articles
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Links
Hormonal markers in breast cancer: coexpression, relationship with pathologic characteristics, and risk factor associations in a population-based study.
Yang XR
,
Pfeiffer RM
,
Garcia-Closas M
,
Rimm DL
,
Lissowska J
,
Brinton LA
,
Peplonska B
,
Hewitt SM
,
Cartun RW
,
Mandich D
,
Sasano H
,
Evans DB
,
Sutter TR
,
Sherman ME
.
Genetic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH, Bethesda, MD 20892-7236, USA. royang@mail.nih.gov
The objective of this study was to evaluate the coexpression patterns of hormonal markers in breast cancer tissue and their relationship with pathologic characteristics and epidemiologic risk factors. We evaluated the expression of 17 markers by immunohistochemistry in 842 invasive breast carcinomas collected in a population-based case-control study conducted in Poland. Based on marker correlations, factor analysis identified four major coexpression patterns (factors): "nuclear receptor factor" [estrogen receptor (ER)-alpha, progesterone receptor, androgen receptor, cyclin D1, and aromatase], "estrogen metabolism/ER-beta factor" (ER-beta, peroxisome proliferator-activated receptor-gamma, steroid sulfatase, estrogen sulfonotransferase, and cytochrome P450 1B1), "HER2 factor" (human epidermal growth factor receptor 2, E-cadherin, cyclooxygenase-2, aromatase, steroid sulfatase), and "proliferation factor" (cytokeratin 5, cytokeratin 5/6, epidermal growth factor receptor, P53). Three of these factors corresponded to molecular subtypes previously defined by expression profiling; however, the estrogen metabolism/ER-beta factor seemed to be distinctive. High scores for this factor were associated with high tumor grade (P heterogeneity = 0.02), younger age at menarche (P heterogeneity = 0.04), lower current body mass index among premenopausal women (P heterogeneity = 0.01), and older age at menopause (P heterogeneity = 0.04). High scores for the proliferation factor were also associated with early menarche (P heterogeneity < 0.0001), and in contrast to the estrogen metabolism/ER-beta factor, higher current body mass index among premenopausal women (P heterogeneity = 0.03). Our analysis of hormonal pathway markers independently confirmed several previously defined molecular subtypes identified by gene expression profiling and augmented these findings by suggesting the existence of additional relationships related to ER-beta and enzymes involved in hormone metabolism.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
MeSH Terms:
Adult
Aged
Aromatase/analysis
Body Mass Index
Breast Neoplasms/chemistry*
Breast Neoplasms/etiology*
Breast Neoplasms/pathology
Case-Control Studies
Estrogen Receptor alpha/analysis
Estrogen Receptor beta/analysis
Estrogens/metabolism
Female
Humans
Immunohistochemistry
Middle Aged
Receptor, Epidermal Growth Factor/analysis
Receptor, erbB-2/analysis
Risk Factors
Tissue Array Analysis
Tumor Suppressor Protein p53/analysis
Substances:
Estrogen Receptor alpha
Estrogen Receptor beta
Estrogens
Tumor Suppressor Protein p53
Aromatase
Receptor, Epidermal Growth Factor
Receptor, erbB-2
PMID: 17968031 [PubMed - indexed for MEDLINE]
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