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The epigenetic silencing of the estrogen receptor (ER) by hypermethylation of the ESR1 promoter is seen predominantly in triple-negative breast cancers in Indian women

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Tumor Biology

Abstract

The proportion of estrogen receptor (ER)-negative and triple-negative (TN) breast cancer in Indian women is higher than that reported in the West, and this difference persists even after their migration to the West. The causes for this significant difference are not entirely clear. Hypermethylation of the ER promoter, an epigenetic alteration, is known to be one of the mechanisms by which the expression of ER is suppressed. Two thirds of breast cancer specimens from an Indian center tested, using the highly sensitive, methylation-specific polymerase chain reaction (MSP) technique, were reported positive. We have used a quantitative assay, the MethyLight, to better assess the extent of methylation in the ESR1 promoter region in 98 breast cancer tumor specimens from Indian women. In addition, the amount of ER transcripts was determined by quantitative reverse transcriptase polymerase chain reaction. Using the stringent cutoff of at least 4% of the target sequence being methylated, 27% of TN tumors were methylated. In addition they demonstrated the highest levels of methylation. In contrast less than 2% ER-positive tumors were hypermethylated. While the proportion of hypermethylated tumors are lower in this study than that estimated using MSP, our results support the notion of increased epigenetic deregulations in ER-negative tumors in general and TN tumors in particular. The development of this assay also permits a rational approach to the selection of patients for clinical trials examining the efficacy of demethylating agents in the treatment of ER-negative breast cancer.

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Acknowledgments

This work was funded by the Nadathur Holdings, Bangalore and the Bagaria Education Trust, Bangalore. The patient enrolment, sample collection, and patient follow-up were coordinated by Ms. Annie Alexander of “Aadhara”, our patient support group. We would also like to acknowledge the excellent technical support provided by Mr. Raju and Ms. Anupama as well as the meticulous collation of clinical information by Ms. Rohini our clinical research associate. Dr Tinku Thomas of the Epidemiology and Biostatistics division of SJRI reviewed the statistical analysis.

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Author notes

  1. Kanu Wahi

    Present address: Dept of Molecular Genetics, Ohio State University, Columbus, OH, 43210, USA

Authors and Affiliations

  1. Division of Molecular Medicine, St. John’s Research Institute, Koramangala, Bangalore, India

    Jyothi S. Prabhu, Kanu Wahi, Aruna Korlimarla & T. S. Sridhar

  2. Department of Pathology, St. John’s Medical College and Hospital, Bangalore, India

    Marjorrie Correa

  3. Department of Surgical Oncology, St. John’s Medical College and Hospital, Bangalore, India

    Suraj Manjunath

  4. Rangadore Memorial Hospital, Bangalore, India

    N. Raman & B. S. Srinath

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  1. Jyothi S. Prabhu
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Correspondence to Jyothi S. Prabhu.

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Prabhu, J.S., Wahi, K., Korlimarla, A. et al. The epigenetic silencing of the estrogen receptor (ER) by hypermethylation of the ESR1 promoter is seen predominantly in triple-negative breast cancers in Indian women. Tumor Biol. 33, 315–323 (2012). https://doi.org/10.1007/s13277-012-0343-1

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