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Estrogen receptor and HER2/neu status affect epigenetic differences of tumor-related genes in primary breast tumors.
Breast Cancer Res. 2008; 10(3):R46.BC

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, RARbeta2, 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.

Authors+Show Affiliations

Department of Molecular Oncology, The John Wayne Cancer Institute, Saint John's Health Center, Santa Monica Blvd, Santa Monica, California 90404, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18485221

Citation

Sunami, Eiji, et al. "Estrogen Receptor and HER2/neu Status Affect Epigenetic Differences of Tumor-related Genes in Primary Breast Tumors." Breast Cancer Research : BCR, vol. 10, no. 3, 2008, pp. R46.
Sunami E, Shinozaki M, Sim MS, et al. Estrogen receptor and HER2/neu status affect epigenetic differences of tumor-related genes in primary breast tumors. Breast Cancer Res. 2008;10(3):R46.
Sunami, E., Shinozaki, M., Sim, M. S., Nguyen, S. L., Vu, A. T., Giuliano, A. E., & Hoon, D. S. (2008). Estrogen receptor and HER2/neu status affect epigenetic differences of tumor-related genes in primary breast tumors. Breast Cancer Research : BCR, 10(3), R46. https://doi.org/10.1186/bcr2098
Sunami E, et al. Estrogen Receptor and HER2/neu Status Affect Epigenetic Differences of Tumor-related Genes in Primary Breast Tumors. Breast Cancer Res. 2008;10(3):R46. PubMed PMID: 18485221.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estrogen receptor and HER2/neu status affect epigenetic differences of tumor-related genes in primary breast tumors. AU - Sunami,Eiji, AU - Shinozaki,Masaru, AU - Sim,Myung-Shin, AU - Nguyen,Sandy L, AU - Vu,Anh-Thu, AU - Giuliano,Armando E, AU - Hoon,Dave S B, Y1 - 2008/05/16/ PY - 2008/01/03/received PY - 2008/03/13/revised PY - 2008/05/16/accepted PY - 2008/5/20/pubmed PY - 2008/11/13/medline PY - 2008/5/20/entrez SP - R46 EP - R46 JF - Breast cancer research : BCR JO - Breast Cancer Res VL - 10 IS - 3 N2 - 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, RARbeta2, 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. SN - 1465-542X UR - https://www.unboundmedicine.com/medline/citation/18485221/Estrogen_receptor_and_HER2/neu_status_affect_epigenetic_differences_of_tumor_related_genes_in_primary_breast_tumors_ L2 - https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr2098 DB - PRIME DP - Unbound Medicine ER -