title: HDAC6 expression is correlated with better survival in breast cancer.
abstract: OBJECTIVE
  The structure and function of chromatin can be altered by modifications to histone. Histone acetylation in vivo is a dynamic reversible process governed by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC6 is a unique isoform among the HDACs, and a gene expression pattern study, with cDNA microarray in MCF-7 cells, showed the HDAC6 gene to be late responsive, estrogen induced, and up-regulated. This led us to hypothesize that there was a link between levels of HDAC6 expression and the metastatic potential of breast cancer and also, therefore, the prognosis of these patients.
  
  
  METHODS
  In the present study, the level of HDAC6 mRNA expression was analyzed with quantitative real-time reverse transcription-PCR, in 135 female patients with invasive breast cancer. HDAC6 protein expression was also determined by immunohistochemistry. An association was sought between HDAC6 expression and various clinicopathologic factors.
  
  
  RESULTS
  HDAC6 mRNA was expressed at significantly higher levels in breast cancer patients with small tumors measuring less than 2 cm, with low histologic grade, and in estrogen receptor alpha- and progesterone receptor-positive tumors. By contrast, no relationship was found between HDAC6 mRNA expression and any of the other clinicopathologic factors, namely, age, menopausal status, and axillary lymph node involvement. Patients expressing high levels of HDAC6 mRNA and protein had a better prognosis than those expressing low levels, in terms of disease-free survival. However, multivariate analysis failed to show that HDAC6 mRNA and protein are an independent prognostic factors for disease-free survival and overall survival. Furthermore, the patients with high levels of HDAC6 mRNA tended to be more responsive to endocrine treatment than those with low levels. Specific HDAC6 staining was found in the nucleus of some normal epithelial cells and in the cytoplasm of the majority of cancer cells. Although postmenopausal patients showed higher HDAC6 protein expression, there were no relationship between protein expression and any other clinicopathologic factors.
  
  
  CONCLUSIONS
  We conclude that the levels of HDAC6 mRNA expression may have potential both as a marker of endocrine responsiveness and also as a prognostic indicator in breast cancer. Additional investigations are warranted concerning the relationship between HDAC6 expression and response to endocrine therapy.
authors.affiliation: Department of Breast and Endocrine Surgery, Nagoya City University Hospital, Nagoya, Japan.
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamashita
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Toyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Omoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ando
authors.forename: Keiko
authors.initials: K
authors.lastname: Mita
authors.forename: Maho
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hayashi
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000032:analysis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D011960:Receptors, Estrogen; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases