J Breast Cancer.  2015 Sep;18(3):249-255. 10.4048/jbc.2015.18.3.249.

Potential Prognostic Value of Histone Deacetylase 6 and Acetylated Heat-Shock Protein 90 in Early-Stage Breast Cancer

• Park Y
• Lee KS
• Park SY
• Kim JH
• Kang EY
• Kim SW
• Eom KY
• Kim JS
• Kim IA

• KMID: 2407572
• DOI: http://doi.org/10.4048/jbc.2015.18.3.249

Abstract

PURPOSE
Histone deacetylase 6 (HDAC6) is an enzyme that deacetylates heat-shock protein 90 (HSP90). Many studies have investigated the role of HDAC6 and HSP90 in tumorigenesis and in the prognosis of cancer patients. This study aimed to evaluate the prognostic value of HDAC6 and acetylated HSP90 (acetyl-HSP90) in a cohort of breast cancer patients.
METHODS
Immunohistochemical analysis of 314 surgical specimens obtained from patients with invasive breast cancer was carried out to assess standard pathologic factors and the expression of HDAC6 and acetyl-HSP90. Statistical analyses were performed to determine the association between HDAC6, acetyl-HSP90, and conventional clinicopathological factors, and the prognostic values of these factors were evaluated.
RESULTS
HDAC6 expression did not show any correlation with other clinicopathological factors, but acetyl-HSP90 was significantly correlated with histologic grade (p=0.001) and the Ki-67 index (p=0.015). HDAC6 and acetyl-HSP90 expression were significantly associated with each other (p=0.047). Although HDAC6 was not prognostic for disease-free survival (DFS), some patients with high expression of HDAC6 experienced recurrence 5 years after diagnosis, while there was no recurrent disease after 5 years in those with low expression. Acetyl-HSP90 was significantly associated with the DFS of all patients (p=0.016) and with high HDAC6 expression (p=0.017), but not with low expression.
CONCLUSION
Expression of HDAC6 and acetyl-HSP90 are correlated. HDAC6 is proposed to be a possible predictive marker of late recurrence, and acetyl-HSP90 has prognostic value in predicting the DFS of breast cancer patients.

Keyword

Breast neoplasms; Disease-free survival; Heat-shock protein 90; Histone deacetylase 6; Prognosis

MeSH Terms

Breast Neoplasms*
Breast*
Carcinogenesis
Cohort Studies
Diagnosis
Disease-Free Survival
Heat-Shock Proteins*
Histone Deacetylases*
Histones*
Humans
Prognosis
Recurrence
Heat-Shock Proteins
Histone Deacetylases
Histones

Figure

• 

  Figure 1 Immunohistochemical analyses of histone deacetylase 6 (HDAC6) and acetylated heat-shock protein 90 (acetyl-HSP90) (×400). (A) Negative for HDAC6. (B) Positive for HDAC6. (C) Negative for acetyl-HSP90. (D) Positive for acetyl-HSP90.

• 

  Figure 2 Kaplan-Meir survival curves for disease-free survival of breast cancer patients based on histone deacetylase 6 expression in total patients (A), estrogen receptor negative (B), and ER-positive (C) group. HDAC6=deacetylase 6; ER=estrogen receptor.

• 

  Figure 3 Kaplan-Meir survival curves for disease-free survival of breast cancer patients based on acetylated heat-shock protein 90 (acetyl-HSP90) level in total patients (A), histone deacetylase 6 (HDAC6) low expression (B), and HDAC6 high expression (C) group.

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