Open Access Highly Accessed Research article

Differential expression of histone deacetylases HDAC1, 2 and 3 in human breast cancer - overexpression of HDAC2 and HDAC3 is associated with clinicopathological indicators of disease progression

Berit Maria Müller1*, Lisa Jana1, Atsuko Kasajima4, Annika Lehmann1, Judith Prinzler1, Jan Budczies1, Klaus-Jürgen Winzer3, Manfred Dietel1, Wilko Weichert2 and Carsten Denkert1

Author Affiliations

1 Institute of Pathology, Charité University Hospital, Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany

2 Institute of Pathology, Heidelberg, Germany

3 Breast Cancer Center, Charité University Hospital, Campus Mitte, Charitéplatz 1 10117, Berlin, Germany

4 Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aobaku, Sendai J980-8574, Miyagi, Japan

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BMC Cancer 2013, 13:215  doi:10.1186/1471-2407-13-215

Published: 30 April 2013

Abstract

Background

In breast cancer, the role of epigenetic alterations including modifications of the acetylation status of histones in carcinogenesis has been an important research focus during the last years. An increased deacetylation of histones leads to increased cell proliferation, cell migration, angiogenesis and invasion. Class 1 histone deacetylases (HDAC) seem to be most important during carcinogenesis.

Methods

The immunhistochemical expression of HDAC1, 2 and 3 was analyzed on tissue microarrays (TMAs) from 238 patients with primary breast cancer. We analyzed the nuclear staining intensity (negative, weak, moderate, strong) as well as the percentage of positive tumor cells and calculated the immunoreactivity score (0–12). Expression was correlated with clinicopathological parameters and patient survival.

Results

In this cohort, we found a differential positive expression of HDAC1, HDAC2 and HDAC3. HDAC2 and HDAC3 expression was significantly higher in less differentiated tumors: HDAC2 (n=207), p<0.001 and HDAC3 (n=220), p<0.001 and correlated with negative hormone receptor status: HDAC2 (n=206), p=0.02 and HDAC3 (n=219), p=0.04. Additionally, a high HDAC2 expression was significantly associated with an overexpression of HER2 (n=203, p=0.005) and the presence of nodal metastasis (n=200, p=0.04).

HDAC1 was highly expressed in hormone receptor positive tumors (n=203; p<0.001).

Conclusion

As a conclusion, our results show that the class-1 HDAC isoenzymes 1, 2 and 3 are differentially expressed in breast cancer. HDAC2 and HDAC3 are strongly expressed in subgroups of tumor with features of a more aggressive tumor type.

Keywords:
HDAC; Breast cancer; Immunohistochemistry