title: HDAC2 overexpression is a poor prognostic factor of breast cancer patients with increased multidrug resistance-associated protein expression who received anthracyclines therapy.
abstract: OBJECTIVE
  Previous studies have revealed the association of multidrug resistance with histone deacetylases inhibitors treatment in cancer cells. But little data were available for the correlation of histone deacetylases and drug-resistant-related proteins in breast cancer tissue. This study aimed to exploring the association of histone deacetylases expression with clinicopathological features, drug-resistant-related proteins, prognosis and therapeutic responses in breast cancer patients.
  
  
  METHODS
  We performed immunohistochemistry to study the expression of HDAC1 and HDAC2 in 226 breast cancer and 34 breast fibroadenoma patients, and the expression of breast cancer resistance protein, P-glycoprotein, lung resistance protein and multidrug resistance protein in 226 breast cancer.
  
  
  RESULTS
  In breast cancer, HDAC2 expression was significantly increased than in fibroadenoma (P = 0.015), and correlated with lymph node metastasis (P = 0.002), advanced clinical stages (P = 0.016) and high histological grade (P = 0.001). Significant positive correlations were found between HDAC2 and Ki67, HDAC1 and multidrug resistance protein, HDAC2 and breast cancer resistance protein, HDAC2 and multidrug resistance protein. HDAC2 positive expression was associated with shorter overall survival (P = 0.035) of breast cancer patients. In addition, HDAC2-positive expression was significantly associated with shorter overall survival in multidrug resistance protein-positive patients (P = 0.034), but not in multidrug resistance protein-negative patients (P = 0.530). HDAC2-positive expression was associated with shorter survival in patients who received chemotherapy containing anthracyclines (overall survival, P = 0.041; disease-free survival, P = 0.084), but not in patients who received chemotherapy without anthracyclines (overall survival, P = 0.679; disease-free survival, P = 0.708).
  
  
  CONCLUSIONS
  HDAC2 overexpression correlated with the metastasis, progression and the increased Ki67, multidrug resistance protein expression in breast cancer, and HDAC2 could be a prognostic factor of breast cancer patients, especially the patients who received anthracyclines therapy.
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China.
authors.forename: Haishan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China.
authors.forename: Zhaojin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China.
authors.forename: Huizhe
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China.
authors.forename: Qiuchen
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China.
authors.forename: Weifan
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China weiminjiecmu@163.com.
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018943:Anthracyclines; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
keywords: breast cancer; chemotherapy; histone deacetylases; multidrug resistance-associated protein; survival analysis