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- Document type:
- journal article
- Author(s):
- Nimmrich, I; Sieuwerts, AM; Meijer-van Gelder, ME; Schwope, I; Bolt-de Vries, J; Harbeck, N; Koenig, T; Hartmann, O; Kluth, A; Dietrich, D; Magdolen, V; Portengen, H; Look, MP; Klijn, JG; Lesche, R; Schmitt, M; Maier, S; Foekens, JA; Martens, JW
- Title:
- DNA hypermethylation of PITX2 is a marker of poor prognosis in untreated lymph node-negative hormone receptor-positive breast cancer patients.
- Abstract:
- BACKGROUND: In this study, we evaluated if PITX2 DNA methylation is a marker for disease recurrence in lymph node-negative (LNN), steroid hormone receptor-positive (HR+) breast cancer patients. In addition, we studied the association between PITX2 DNA methylation and PITX2 gene expression. PATIENTS AND METHODS: PITX2 DNA-methylation was measured in tumor tissue from 412 LNN/HR+ breast cancer patients who had not received any adjuvant systemic treatment. In addition, PITX2 DNA-methylation and mRNA expression was evaluated in 32 breast cancer cell lines. RESULTS: In univariate Cox regression analysis, DNA-methylation of PITX2 as a continuous variable was associated with early distant metastasis (HR = 1.71; P< 0.01) and poor overall survival (HR = 1.71; P< 0.01). In multivariate analysis together with the established prognostic factors age, tumor size and tumor grade, and steroid hormone receptor levels, both associations retained their significance (for MFS, HR = 1.74; P< 0.01; for OS, HR = 1.46; P = 0.02). In the breast cancer cell lines, PITX2 DNA methylation was inversely association with PITX2A and PITX2B mRNA expression (P< 0.01). CONCLUSIONS: Hypermethylation of PITX2 is, in cell lines, negatively associated with PITX2 mRNA expression and, in clinical specimens, positively associated with breast cancer disease progression.
- Journal title abbreviation:
- Breast Cancer Res Treat
- Year:
- 2008
- Journal volume:
- 111
- Journal issue:
- 3
- Pages contribution:
- 429-37
- Language:
- eng
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/17965955
- Print-ISSN:
- 0167-6806
- TUM Institution:
- Frauenklinik und Poliklinik
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