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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2012

01-09-2012 | Translational Research and Biomarkers

Clinical Significance of Promoter Hypermethylation of ERβ and RARβ2 in Tumor and Serum DNA in Indian Breast Cancer Patients

Authors: Sameer Mirza, PhD, Gayatri Sharma, PhD, Rajinder Parshad, MS, Anurag Srivastava, MS, Siddartha Datta Gupta, MD, Ranju Ralhan, PhD

Published in: Annals of Surgical Oncology | Issue 9/2012

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Abstract

Purpose

To determine concordance of promoter hypermethylation of ERβ (estrogen receptor β) and RARβ2 (retinoic acid receptor β2) in tumor and circulating DNA of Indian breast cancer patients and their association with clinicopathologic parameters and disease prognosis.

Methods

ERβ and RARβ2 methylation was analyzed by methylation-specific PCR in the tumors and circulating DNA of 100 patients with invasive ductal breast carcinoma. Promoter hypermethylation was associated with the expression of the encoded protein in tumors by immunohistochemistry, and their prognostic utility was explored in a follow-up study.

Results

Significant correlation was observed between promoter hypermethylation of ERβ (r = + 0.77; p ≤ 0.001) and RARβ2 (r = + 0.85; p ≤ 0.001) in tumors and paired sera. No association was found between ERβ and RARβ2 promoter hypermethylation and loss of protein expression. Kaplan–Meier survival curve showed loss of ERβ expression, and RARβ2 promoter hypermethylation was associated with poor overall survival (OS) (p = 0.03, p = 0.001). Breast cancer patients showing concurrent hypermethylation of ERβ and RARβ2 had a significantly shorter median OS (p = 0.02), underscoring that hypermethylation of these two genes may serve as an adverse prognosticator for breast carcinoma.

Conclusions

Methylation status of ERβ and RARβ2 in serum could potentially be used to predict invasive ductal breast carcinoma. Furthermore, concurrent ERβ and RARβ2 methylation as well as loss of ERβ expression may serve as a good prognostic marker.
Appendix
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Metadata
Title
Clinical Significance of Promoter Hypermethylation of ERβ and RARβ2 in Tumor and Serum DNA in Indian Breast Cancer Patients
Authors
Sameer Mirza, PhD
Gayatri Sharma, PhD
Rajinder Parshad, MS
Anurag Srivastava, MS
Siddartha Datta Gupta, MD
Ranju Ralhan, PhD
Publication date
01-09-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 9/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2323-5

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