Estrogen Receptor Phenotypes Defined by Gene Expression Profiling

Introduction. Accurate evaluation of estrogen and progesterone receptors and HER2 is critical when diagnosing invasive breast cancer for optimal treatment. The current evaluation method is via immunohistochemistry (IHC). In this paper, we compared results of ER, PR, and HER2 from microarray gene expression to IHC in 81 fresh breast cancer specimens. Methods. Gene expression profiling was performed using the GeneChip Human Genome U133 Plus 2.0 arrays (Affymetrix Inc). Immunohistochemical staining for estrogen receptor, progesterone receptor, and HER2 status was performed using standard methods at a CAP-accredited pathology laboratory. Concordance rates, agreement measures, and kappa scores were calculated for both methods. Results. For ER, Kappa score was 0.918 (95% CI, 0.77.3–1.000) and concordance rate was 97.5% (95% CI, 91.4%–99.7%). For PR, Kappa score was 0.652 (95% CI, 0.405–0.849) and concordance rate was 86.4% (95% CI, 77%–93%). For HER2, Kappa score was 0.709 (95% CI, 0.428–0.916) and concordance rate was 97.5% (95% CI, 91.4%–99.7%). Conclusion. Our results are in line with the available evidence with the concordance rate being the lowest for the progesterone receptor. In general, microarray gene expression and IHC proved to have high concordance rates. Several factors can increase the discordance rate such as differences in sample processing.

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Auto-regulation of estrogen receptor subtypes and gene expression profiling of 17β-estradiol action in the neuroendocrine axis of male goldfish

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2007.10.013 ◽

2008 ◽

Vol 283 (1-2) ◽

pp. 38-48 ◽

Cited By ~ 95

Author(s):

V.L. Marlatt ◽

C.J. Martyniuk ◽

D. Zhang ◽

H. Xiong ◽

J. Watt ◽

...

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Receptor Subtypes ◽

17Β Estradiol ◽

Neuroendocrine Axis

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Estrogen Receptor (ESR1) mRNA Expression and Benefit From Tamoxifen in the Treatment and Prevention of Estrogen Receptor–Positive Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2010.32.9615 ◽

2011 ◽

Vol 29 (31) ◽

pp. 4160-4167 ◽

Cited By ~ 71

Author(s):

Chungyeul Kim ◽

Gong Tang ◽

Katherine L. Pogue-Geile ◽

Joseph P. Costantino ◽

Frederick L. Baehner ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Estrogen Receptor ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Tamoxifen Resistance ◽

Linear Predictor ◽

Treatment And Prevention ◽

Er Positive ◽

Positive Breast Cancer

Purpose Several mechanisms have been proposed to explain tamoxifen resistance of estrogen receptor (ER) –positive tumors, but a clinically useful explanation for such resistance has not been described. Because the ER is the treatment target for tamoxifen, a linear association between ER expression levels and the degree of benefit from tamoxifen might be expected. However, such an association has never been demonstrated with conventional clinical ER assays, and the ER is currently used clinically as a dichotomous marker. We used gene expression profiling and ER protein assays to help elucidate molecular mechanism(s) responsible for tamoxifen resistance in breast tumors. Patients and Methods We performed gene expression profiling of paraffin-embedded tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) trials that tested the worth of tamoxifen as an adjuvant systemic therapy (B-14) and as a preventive agent (P-1). This was a retrospective subset analysis based on available materials. Results In B-14, ESR1 was the strongest linear predictor of tamoxifen benefit among 16 genes examined, including PGR and ERBB2. On the basis of these data, we hypothesized that, in the P-1 trial, a lower level of ESR1 mRNA in the tamoxifen arm was the main difference between the two study arms. Only ESR1 was downregulated by more than two-fold in ER-positive cancer events in the tamoxifen arm (P < .001). Tamoxifen did not prevent ER-positive tumors with low levels of ESR1 expression. Conclusion These data suggest that low-level expression of ESR1 is a determinant of tamoxifen resistance in ER-positive breast cancer. Strategies should be developed to identify, treat, and prevent such tumors.

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Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-α-positive human cells

Environmental Research ◽

10.1016/j.envres.2005.05.004 ◽

2006 ◽

Vol 100 (1) ◽

pp. 86-92 ◽

Cited By ~ 45

Author(s):

David W. Singleton ◽

Yuxin Feng ◽

Jun Yang ◽

Alvaro Puga ◽

Adrian V. Lee ◽

...

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Bisphenol A ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Estrogen Receptor Α ◽

Human Cells

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The use of gene-expression profiling to better understand the clinical heterogeneity of estrogen receptor positive breast cancers and tamoxifen response

Critical Reviews in Oncology/Hematology ◽

10.1016/j.critrevonc.2006.09.005 ◽

2007 ◽

Vol 61 (3) ◽

pp. 187-194 ◽

Cited By ~ 33

Author(s):

Sherene Loi ◽

Martine Piccart ◽

Christos Sotiriou

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Clinical Heterogeneity ◽

Breast Cancers ◽

Estrogen Receptor Positive ◽

Tamoxifen Response

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Therapeutic predictors of neoadjuvant endocrine therapy response in estrogen receptor-positive breast cancer with reference to optimal gene expression profiling

Breast Cancer Research and Treatment ◽

10.1007/s10549-018-4933-5 ◽

2018 ◽

Vol 172 (2) ◽

pp. 353-362 ◽

Cited By ~ 5

Author(s):

Lisa Goto-Yamaguchi ◽

Mutsuko Yamamoto-Ibusuki ◽

Yutaka Yamamoto ◽

Yoshitaka Fujiki ◽

Mai Tomiguchi ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Estrogen Receptor ◽

Gene Expression Profiling ◽

Endocrine Therapy ◽

Expression Profiling ◽

Therapy Response ◽

Neoadjuvant Endocrine Therapy ◽

Estrogen Receptor Positive ◽

Positive Breast Cancer

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Custom microarray for glycobiologists: considerations for glycosyltransferase gene expression profiling

Biochemical Society Symposium ◽

10.1042/bss0690135 ◽

2002 ◽

Vol 69 ◽

pp. 135-142 ◽

Cited By ~ 12

Author(s):

Elena M. Comelli ◽

Margarida Amado ◽

Steven R. Head ◽

James C. Paulson

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Affymetrix Genechip ◽

Microarray Technology ◽

Gene Arrays ◽

Glycosyltransferase Gene

The development of microarray technology offers the unprecedented possibility of studying the expression of thousands of genes in one experiment. Its exploitation in the glycobiology field will eventually allow the parallel investigation of the expression of many glycosyltransferases, which will ultimately lead to an understanding of the regulation of glycoconjugate synthesis. While numerous gene arrays are available on the market, e.g. the Affymetrix GeneChip® arrays, glycosyltransferases are not adequately represented, which makes comprehensive surveys of their gene expression difficult. This chapter describes the main issues related to the establishment of a custom glycogenes array.

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