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[Cancer Research 66, 29-33, January 1, 2006]
© 2006 American Association for Cancer Research


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Breast Cancer DNA Methylation Profiles in Cancer Cells and Tumor Stroma: Association with HER-2/neu Status in Primary Breast Cancer

Heidi Fiegl1,5, Simone Millinger1, Georg Goebel2, Elisabeth Müller-Holzner1, Christian Marth1, Peter W. Laird3,4 and Martin Widschwendter1,5

Departments of 1 Obstetrics and Gynecology, and 2 Medical Statistics, Informatics, and Health Economics, Innsbruck Medical University, Innsbruck, Austria; Departments of 3 Biochemistry and Molecular Biology, and 4 Surgery, University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California; and 5 Department of Gynaecological Oncology, Institute for Women's Health, University College London, United Kingdom

Requests for reprints: Martin Widschwendter, Department of Gynaecological Oncology, Institute for Women's Health, University College London, EGA Hospital, 2nd Floor, Huntley Street, London, WC1E 6DH, United Kingdom. Phone: 44-20-7380-6807; Fax: 44-20-7380-9748; E-mail: M.Widschwendter{at}ucl.ac.uk.

The HER-2/neu gene is amplified and overexpressed in 20% to 30% of invasive breast carcinomas and is associated with increased metastatic potential and less tamoxifen sensitivity. We generated the DNA methylation profiles of 143 human breast tumors and found significant differences in HER-2/neu expression and DNA methylation of five genes. For three of these five genes [PGR (coding for the progesterone receptor), HSD17B4 (coding for type 4 17-ß-hydroxysteroid dehydrogenase, an enzyme that mainly degrades active 17-ß-estradiol into inactive metabolites), and CDH13 (coding for H-cadherin)] a higher prevalence of DNA methylation in HER-2/neu-positive cancers was confirmed in an independent set of microdissected primary breast cancers. DNA methylation was not only present in cancer cells but also in the tumor stroma fraction. Of the isolated fractions in HER-2/neu-positive versus -negative cancers, 27.1% versus 10.5%, respectively, showed DNA methylation of the five genes (P = 0.011, Fisher's exact test). In Her-2++/+++ breast cancers, HSD17B4 mRNA expression was inversely associated with HSD17B4 methylation (P = 0.04). These data support the view that in addition to HER-2/neu-associated signaling, epigenetic changes in cancer as well as in tumor stroma cells might attribute to the specific biological features of HER-2/neu-positive cancers. (Cancer Res 2006; 66(1): 29-33)




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2006 by the American Association for Cancer Research.