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Promoter hypermethylation in sentinel lymph nodes as a marker for breast cancer recurrence

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Abstract

Purpose Promoter methylation of tumor suppressor genes in histologically negative sentinel lymph nodes (HNSN) of early stage breast cancer patients has not been extensively studied. This study evaluates the methylation frequency and pattern in HNSN to determine if detection of hypermethylation of one or more genes is associated with an increased recurrence risk in node negative breast cancer. Experimental design In 1998, a prospective study of patients with early stage breast cancer and HNSN was initiated in order to correlate sentinel node analysis with clinical outcome. Nodal tissue was selected from 120 HNSN patients for methylation analysis in at least one and up to six sentinel nodes using a panel of nine genes. Corresponding primary breast tumors from 79 patients were also evaluated for hypermethylation. Methylation analysis was performed using nested Methylation Sensitive PCR (n-MSP). Logistical regression was used to evaluate the relationship between clinical recurrence and methylation status. Results Over a median follow-up of 79 months, 13 of the 120 patients had clinical recurrence. Hypermethylation of genes was frequently observed in HNSN, but there was no correlation of methylation pattern and clinical recurrence. However, increased frequency of gene methylation of the primary tumor correlated with clinical recurrence. Conclusions Although hypermethylation of multiple genes occurs frequently in HNSN of breast cancer patients, it is not associated with breast cancer recurrence in the first 7 years of clinical follow-up.

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Acknowledgements

This work was funded by the Flight Attendant Medical Research Institute (FAMRI), the Department of Defense Breast Cancer Research Program (BCRP) of the Office of Congressionally Directed Medical Research Programs (CDMRP), the NIH CA88843, and the Belfer and Avon Foundations. We extend our gratitude to agencies like these that enable scientific pursuits for the benefit of all cancer patients.

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Authors and Affiliations

  1. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, 1650 Orleans Street, Cancer Research Building I, Room 290, Baltimore, MD, 21231, USA

    Hetty E. Carraway

  2. Department of Internal Medicine, Division of Oncology, Beijing, China

    Shelun Wang

  3. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, 550 North Broadway, Suite 1111, Baltimore, MD, 21205, USA

    Amanda Blackford

  4. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, 1650 Orleans Street, Cancer Research Building I, Baltimore, MD, 21231, USA

    Mingzho Guo, Penny Powers, Stacie Jeter, Nancy E. Davidson & James G. Herman

  5. Department of Pathology, Johns Hopkins Hospital, 401 North Broadway, Room 2242, Baltimore, MD, 21231, USA

    Pedram Argani

  6. Department of Surgery, Johns Hopkins Hospital, 601 North Caroline Street, Baltimore, MD, 21287, USA

    Kyle Terrell

  7. Department of Surgery, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD, 21287, USA

    Julie R. Lange

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  1. Hetty E. Carraway
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  2. Shelun Wang
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Correspondence to Hetty E. Carraway.

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An invited commentary to this article can be found at doi:10.1007/s10549-008-0106-2.

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Carraway, H.E., Wang, S., Blackford, A. et al. Promoter hypermethylation in sentinel lymph nodes as a marker for breast cancer recurrence. Breast Cancer Res Treat 114, 315–325 (2009). https://doi.org/10.1007/s10549-008-0004-7

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