Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis

Impaired histone acetylation was recognized to be involved in carcinogenesis. Furthermore, histone deacetylase (HDAC) inhibitors induce differentiation of breast cancer cells and inhibit tumour growth. These results prompted us to study HDAC-1 and -3 expression in breast tumours to establish their p...

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Published in:Breast cancer research and treatment 2005-03, Vol.90 (1), p.15-23
Main Authors: KRUSCHE, Claudia A, WÜLFING, Pia, KERSTING, Christian, VLOET, Anne, BÖCKER, Werner, KIESEL, Ludwig, BEIER, Henning M, ALFER, Joachim
Format: Article
Language:English
Subjects:
Biological and medical sciences
Biomarkers, Tumor - metabolism
Breast cancer
Breast Neoplasms - mortality
Breast Neoplasms - pathology
Cancer research
Cell Differentiation
Disease-Free Survival
Female
Follow-Up Studies
Gene expression
Germany - epidemiology
Gynecology. Andrology. Obstetrics
Histone Deacetylases - metabolism
Humans
Immunohistochemistry
Mammary gland diseases
Medical sciences
Medical treatment
Middle Aged
Proportional Hazards Models
Proteins
Survival Rate
Tissue Array Analysis
Tumors
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Summary:Impaired histone acetylation was recognized to be involved in carcinogenesis. Furthermore, histone deacetylase (HDAC) inhibitors induce differentiation of breast cancer cells and inhibit tumour growth. These results prompted us to study HDAC-1 and -3 expression in breast tumours to establish their potential therapeutic and prognostic significance. HDAC-1 und HDAC-3 protein expression was analyzed immunohistochemically on a tissue microarray (TMA) containing 600 core biopsies from 200 patients. HDAC-1 and -3 expression was correlated to steroid hormone receptor-, Her2/neu- and proliferation status of tumours as well as to overall and disease free survival. Moderate or strong nuclear immunoreactivity for HDAC-1 was observed in 39.8% and for HDAC-3 in 43.9% of breast carcinomas. HDAC-1 and -3 expression correlated significantly with oestrogen and progesterone receptor expression (both p< 0.001). HDAC-1 expression predicted significantly better disease free survival (DFS: p=0.044), in particular, in patients with small tumours of all differentiation types (DFS: p=0.016). Multivariate analysis demonstrated that HDAC-1 is an independent prognostic marker. Our data suggest that evaluation of HDAC-1 protein expression enables a more precise assessment of the prognosis of breast cancer patients. Thus, HDAC-1 expression analysis might be clinically useful to facilitate an individual, risk-directed, adjuvant systemic therapy in breast cancer patients.
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-004-1668-2