Skip to main content

Advertisement

Log in

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

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • RL Momparler (2003) ArticleTitleCancer epigenetics Oncogene 22 6479–6483 Occurrence Handle14528271 Occurrence Handle1:CAS:528:DC%2BD3sXnsl2rsrY%3D

    PubMed  CAS  Google Scholar 

  • S Thiagalingam KH Cheng H Lee N Mineva A Thiagalingam JF Ponte (2003) ArticleTitleHistone deacetylases: unique players in shaping the epigenetic histone code Ann NY Acad Sci 983 84–100 Occurrence Handle10.1111/j.1749-6632.2003.tb05964.x Occurrence Handle12724214 Occurrence Handle1:CAS:528:DC%2BD3sXjt1yrs7g%3D

    Article  PubMed  CAS  Google Scholar 

  • L Yan X Yang NE Davidson (2001) ArticleTitleRole of DNA methylation and histone acetylation in steroid receptor expression in breast cancer J Mammary Gland Biol Neoplasia 6 183–192 Occurrence Handle11501578 Occurrence Handle1:STN:280:DC%2BD3MvlsFemsQ%3D%3D

    PubMed  CAS  Google Scholar 

  • WD Cress E Seto (2000) ArticleTitleHistone deacetylases, transcriptional control, and cancer J Cell Physiol 184 1–16 Occurrence Handle10825229 Occurrence Handle1:CAS:528:DC%2BD3cXjvFynur4%3D

    PubMed  CAS  Google Scholar 

  • G Lagger A Doetzlhofer B Schuettengruber E Haidweg E Simboeck J Tischler S Chiocca G Suske H Rotheneder E Wintersberger C Seiser (2003) ArticleTitleThe tumor suppressor p53 and histone deacetylase 1 are antagonistic regulators of the cyclin-dependent kinase inhibitor p21/WAF1/CIP1 gene Mol Cell Biol 23 2669–2679 Occurrence Handle12665570 Occurrence Handle1:CAS:528:DC%2BD3sXktV2lsbo%3D

    PubMed  CAS  Google Scholar 

  • G Lagger D O’Carroll M Rembold H Khier B Schuettengruber C Hauser R Brunmeir T Jenuwein C Seiser (2002) ArticleTitleEssential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression EMBO J 21 2672–2681 Occurrence Handle12032080 Occurrence Handle1:CAS:528:DC%2BD38XkvV2is70%3D

    PubMed  CAS  Google Scholar 

  • T Davis C Kennedy YE Chiew CL Clarke A Fazio Particlede (2000) ArticleTitleHistone deacetylase inhibitors decrease proliferation and modulate cell cycle gene expression in normal mammary epithelial cells Clin Cancer Res 6 4334–4342 Occurrence Handle11106251 Occurrence Handle1:CAS:528:DC%2BD3cXovVSgurY%3D

    PubMed  CAS  Google Scholar 

  • JC Keen L Yan KM Mack C Pettit D Smith D Sharma NE Davidson (2003) ArticleTitleA novel histone deacetylase inhibitor, scriptaid, enhances expression of functional estrogen receptor alpha (ER) in ER negative human breast cancer cells in combination with 5-aza-2′-deoxycytidine Breast Cancer Res Treat 81 177–186 Occurrence Handle14620913 Occurrence Handle1:CAS:528:DC%2BD3sXotVyqtrY%3D

    PubMed  CAS  Google Scholar 

  • ER Jang SJ Lim ES Lee G Jeong TY Kim YJ Bang JS Lee (2004) ArticleTitleThe histone deacetylase inhibitor trichostatin A sensitizes oestrogen receptor α-negative breast cancer cells to tamoxifen Oncogene 23 1724–1736 Occurrence Handle14676837 Occurrence Handle1:CAS:528:DC%2BD2cXhslGisbw%3D

    PubMed  CAS  Google Scholar 

  • L Fuino P Bali S Wittmann S Donapaty F Guo H Yamaguchi HG Wang P Atadja K Bhalla (2003) ArticleTitleHistone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B Mol Cancer Ther 2 971–984 Occurrence Handle14578462 Occurrence Handle1:CAS:528:DC%2BD3sXosVCqt7g%3D

    PubMed  CAS  Google Scholar 

  • DM Vigushin S Ali PE Pace N Mirsaidi K Ito I Adcock RC Coombes (2001) ArticleTitleTrichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo Clin Cancer Res 7 971–976 Occurrence Handle11309348 Occurrence Handle1:CAS:528:DC%2BD3MXjs1eltrw%3D

    PubMed  CAS  Google Scholar 

  • C Kuperwasser J Pinkas GB Hurlbut SP Naber DJ Jerry (2000) ArticleTitleCytoplasmic sequestration and functional repression of p53 in the mammary epithelium is reversed by hormonal treatment Cancer Res 60 2723–2729 Occurrence Handle10825147 Occurrence Handle1:CAS:528:DC%2BD3cXjsF2gtbw%3D

    PubMed  CAS  Google Scholar 

  • HS Zhang DC Dean (2001) ArticleTitleRb-mediated chromatin structure regulation and transcriptional repression Oncogene 20 3134–3138 Occurrence Handle11420730 Occurrence Handle1:CAS:528:DC%2BD3MXks1Glu7w%3D

    PubMed  CAS  Google Scholar 

  • KB Glaser J Li MJ Staver RQ Wie DH Albert SK Davidsen (2003) ArticleTitleRole of class I and class II histone deacetylases in carcinoma cells using siRNA Biochem Biophy Res Commun 310 529–536 Occurrence Handle1:CAS:528:DC%2BD3sXns1Krs7o%3D

    CAS  Google Scholar 

  • MG Guenther O Barak MA Lazar (2001) ArticleTitleThe SMRT and N-CoR corepressors are activating cofactors for histone deacetylase 3 Mol Cell Biol 21 6091–6101 Occurrence Handle11509652 Occurrence Handle1:CAS:528:DC%2BD3MXmsFKmtr0%3D

    PubMed  CAS  Google Scholar 

  • RI Yarden LC Brody (1999) ArticleTitleBRCA1 interacts with components of the histone deacetylase complex Proc Natl Acad Sci USA 96 4983–4988 Occurrence Handle10220405 Occurrence Handle1:CAS:528:DyaK1MXjtVKmsbs%3D

    PubMed  CAS  Google Scholar 

  • J Kononen L Bubendorf A Kallioniemi M Barlund P Schraml S Leighton J Torhorst MJ Milhatsch G Sauter OP Kallioniemi (1998) ArticleTitleTissue microarrays for high-throughput molecular profiling of tumor specimens Nat Med 4 844–847 Occurrence Handle1:CAS:528:DyaK1cXktlKntr8%3D Occurrence Handle9662379

    CAS  PubMed  Google Scholar 

  • P Wülfing R Diallo C Müller C Wülfing C Poremba A Heinecke A Rody RR Greb W Böcker L Kiesel (2003) ArticleTitleAnalysis of cyclooxygenase-2 expression in human breast cancer: high throughput tissue microarray analysis J Cancer Res Clin Oncol 129 375–382 Occurrence Handle12884024

    PubMed  Google Scholar 

  • A Reiner B Neumeister J Spona G Reiner M Schemper R Jakesz (1990) ArticleTitleImmunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer Cancer Res 50 1057–1061

    Google Scholar 

  • C Poremba W Boecker H Willenbring KL Schafer F Otterbach H Burger R Diallo B Dockhorn-Dworniczak (1998) ArticleTitleTelomerase activity in human proliferative breast lesions Int J Oncol 12 641–648 Occurrence Handle9472105 Occurrence Handle1:CAS:528:DyaK1cXitVSrsL8%3D

    PubMed  CAS  Google Scholar 

  • Altman DG: Chi square test for trend. In: Practical Statistics for Medical Research. Chapman & Hall, London, 1995, pp 261–265.

  • G Kouraklis S Theocharis (2002) ArticleTitleHistone deacetylase inhibitors and anticancer therapy Curr Med Chem Anti-Canc Agents 2 477–484 Occurrence Handle1:CAS:528:DC%2BD38Xksl2ju70%3D

    CAS  Google Scholar 

  • A Goldhirsch JH Glick RD Gelber AS Coates HJ Senn (2001) ArticleTitleMeeting highlights: international consensus panel on the treatment of primary breast cancer J Clin Oncol 19 3817–3827 Occurrence Handle11559719 Occurrence Handle1:STN:280:DC%2BD3Mrht1Slsw%3D%3D

    PubMed  CAS  Google Scholar 

  • A Hoos MJ Urist A Stojadinovic S Mastorides ME Dudas DHJ Leung D Kuo MF Brennan JL Lewis C Cordon-Cardo (2001) ArticleTitleValidation of tissue microarrays for immunohistochemical profiling of cancer specimens using the example of human fibroblastic tumours Am J Pathol 158 1245–1251 Occurrence Handle1:CAS:528:DC%2BD3MXjtVWhsLc%3D Occurrence Handle11290542

    CAS  PubMed  Google Scholar 

  • LJ van’t Veer H Dai MJ Vijver Particlevande YD He AAM Hart M Mao HL Peterse K Kooy Particlevander MJ Marton AT Witteveen GJ Schreiber RM Kerkhoven C Roberts PS Linsley R Bernards SH Friend (2002) ArticleTitleGene expression profiling predicts clinical outcome of breast cancer Nature 415 530–536 Occurrence Handle10.1038/415530a Occurrence Handle11823860

    Article  PubMed  Google Scholar 

  • D Santini C Ceccarelli M Taffurelli S Pileri D Marrano (1996) ArticleTitleDifferentiation pathways in primary invasive breast carcinoma as suggested by intermediate filament and biopathological marker expression J Pathol 179 386–391 Occurrence Handle8869285 Occurrence Handle1:STN:280:DyaK2s%2Fit12htw%3D%3D

    PubMed  CAS  Google Scholar 

  • RB Clarke (2003) ArticleTitleSteroid receptors and proliferation in human breast Steroids 68 789–794 Occurrence Handle14667969 Occurrence Handle1:CAS:528:DC%2BD3sXps1Oltb0%3D

    PubMed  CAS  Google Scholar 

  • H Kawai H Li S Avraham S Jiang HK Avraham (2003) ArticleTitleOver expression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of oestrogen receptor alpha Int J Cancer 107 353–358 Occurrence Handle14506733 Occurrence Handle1:CAS:528:DC%2BD3sXos1Gns78%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Claudia A. Krusche.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krusche, C.A., Wülfing, P., Kersting, C. et al. Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis. Breast Cancer Res Treat 90, 15–23 (2005). https://doi.org/10.1007/s10549-004-1668-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-004-1668-2

Keywords

Navigation