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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

ESR1gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients

Authors: Joaquina Martínez-Galán, Blanca Torres-Torres, María Isabel Núñez, Jesús López-Peñalver, Rosario Del Moral, José Mariano Ruiz De Almodóvar, Salomón Menjón, Ángel Concha, Clara Chamorro, Sandra Ríos, Juan Ramón Delgado

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

Tumor expression of estrogen receptor (ER) is an important marker of prognosis, and is predictive of response to endocrine therapy in breast cancer. Several studies have observed that epigenetic events, such methylation of cytosines and deacetylation of histones, are involved in the complex mechanisms that regulate promoter transcription. However, the exact interplay of these factors in transcription activity is not well understood. In this study, we explored the relationship between ER expression status in tumor tissue samples and the methylation of the 5′ CpG promoter region of the estrogen receptor gene (ESR1) isolated from free circulating DNA (fcDNA) in plasma samples from breast cancer patients.

Methods

Patients (n = 110) with non-metastatic breast cancer had analyses performed of ER expression (luminal phenotype in tumor tissue, by immunohistochemistry method), and the ESR1-DNA methylation status (fcDNA in plasma, by quantitative methylation specific PCR technique).

Results

Our results showed a significant association between presence of methylated ESR1 in patients with breast cancer and ER negative status in the tumor tissue (p = 0.0179). There was a trend towards a higher probability of ESR1-methylation in those phenotypes with poor prognosis i.e. 80% of triple negative patients, 60% of HER2 patients, compared to 28% and 5.9% of patients with better prognosis such as luminal A and luminal B, respectively.

Conclusion

Silencing, by methylation, of the promoter region of the ESR1 affects the expression of the estrogen receptor protein in tumors of breast cancer patients; high methylation of ESR1-DNA is associated with estrogen receptor negative status which, in turn, may be implicated in the patient’s resistance to hormonal treatment in breast cancer. As such, epigenetic markers in plasma may be of interest as new targets for anticancer therapy, especially with respect to endocrine treatment.
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Metadata
Title
ESR1gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients
Authors
Joaquina Martínez-Galán
Blanca Torres-Torres
María Isabel Núñez
Jesús López-Peñalver
Rosario Del Moral
José Mariano Ruiz De Almodóvar
Salomón Menjón
Ángel Concha
Clara Chamorro
Sandra Ríos
Juan Ramón Delgado
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-59

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