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Breast Cancer Research
Published in: Breast Cancer Research 3/2008

Open Access 01-06-2008 | Research article

Estrogen receptor and HER2/neu status affect epigenetic differences of tumor-related genes in primary breast tumors

Authors: Eiji Sunami, Masaru Shinozaki, Myung-Shin Sim, Sandy L Nguyen, Anh-Thu Vu, Armando E Giuliano, Dave SB Hoon

Published in: Breast Cancer Research | Issue 3/2008

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Abstract

Introduction

Estrogen receptor (ER)-positive breast cancers are considered prognostically more favorable than ER-negative tumors, whereas human epidermal growth factor receptor (HER)2/neu-positive breast cancers are associated with worse prognosis. The objective of the present study was to determine whether ER-positive and ER-negative status relates to epigenetic changes in breast cancer-related genes. To evaluate epigenetic differences in tumor-related genes relating to ER and HER2/neu status of primary tumors, we examined the promoter methylation status of the promoter region CpG islands of eight major breast tumor-related genes (RASSF1A, CCND2, GSPT1, TWIST, APC, NES1, RARβ2, and CDH1).

Methods

Paired ER-positive (n = 65) and ER-negative (n = 65) primary breast tumors (n = 130) matched for prognostic factors were assessed. DNA was extracted from paraffin-embedded tumor tissue after microdissection, and methylation-specific PCR and capillary-array electrophoresis analysis were performed.

Results

In early stages of tumor progression (T1 and N0), RASSF1A and CCND2 were significantly (P < 0.05) more methylated in ER-positive than in ER-negative tumors. GSTP1 hypermethylation was more frequent in the lymph node metastasis positive group than in the negative group. Double negative (ER-negative, HER2/neu-negative) breast cancers had significantly lesser frequencies of RASSF1A, GSTP1, and APC methylation (P < 0.0001, P < 0.0001, and P = 0.0035, respectively). Both ER and HER2/neu status correlated independently with these epigenetic alterations.

Conclusion

We demonstrated significant differences in tumor-related gene methylation patterns relevant to ER and HER2/neu status of breast tumors. This may be of significance in the assessment of targeted therapy resistance related to ER and HER2/neu status in breast cancer patients.
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Metadata
Title
Estrogen receptor and HER2/neu status affect epigenetic differences of tumor-related genes in primary breast tumors
Authors
Eiji Sunami
Masaru Shinozaki
Myung-Shin Sim
Sandy L Nguyen
Anh-Thu Vu
Armando E Giuliano
Dave SB Hoon
Publication date
01-06-2008
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2008
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2098

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