title: Expression of histone deacetylases in diffuse large B-cell lymphoma and its clinical significance.
abstract: BACKGROUND
  Histone deacetylase inhibitors are a new class of drugs used in treatment of malignant tumors. Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma, and it accounts for more than 40% of all B-cell lymphomas. In this study, we aimed to determine the expression patterns of histone deacetylases (HDACs) in DLBCL, to examine whether HDAC expression patterns differ among cases, and to assess whether these findings have clinical significance.
  
  
  METHODS
  We selected 91 cases of DLBCL diagnosed at St. Vincent Hospital, The Catholic University of Korea, from 2001-2012. We performed a pathology slide review and collected clinical data including age, sex, tumor site, survival time, and mortality. Immunohistochemical analysis was performed using primary antibodies for HDACs, including HDAC1 and 2 of class I, HDAC4 and 5 of class IIa, and HDAC6 of class IIb. Expression site was determined to be nuclear, cytoplasmic, or both. Staining intensities were graded as low and high. We assessed correlations between HDAC expression levels and clinical data and survival analysis.
  
  
  RESULTS
  Of the 91 cases examined, 46 (50.5%) were men and 45 (49.5%) were women. Most of the patients were elderly, and 74 (81.3%) cases were older than 46 y. Forty-six (50.5%) cases showed lymph node involvement, and 45 (49.5%) cases showed lymphoma at extranodal sites. In nodal lymphoma, staining was strongly positive for HDAC2, whereas staining was weak or negative for HDAC4; however, there was no significant correlation with survival. But nodal lymphoma cases with high nuclear expression of HDAC2 and nodal lymphoma cases with high nuclear expression of HDAC2 and low nuclear expression of HDAC4 showed significantly shorter survival times compared with other cases.
  
  
  CONCLUSIONS
  High nuclear expression of HDAC2 may play an important role in survival of DLBCL patients, especially in those with nodal lymphoma, which is associated with a shorter survival time. Our results may have important implications for treatment of DLBCL by epigenetic regulation.
authors: 1. Department of Hospital Pathology, St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors: Sung Hak
authors: SH
authors: Lee
authors: 2. Department of Hospital Pathology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
authors: Changyoung
authors: C
authors: Yoo
authors: 2. Department of Hospital Pathology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
authors: Soyoung
authors: S
authors: Im
authors: 2. Department of Hospital Pathology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
authors: Ji-Han
authors: JH
authors: Jung
authors: 2. Department of Hospital Pathology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
authors: Hyun Joo
authors: HJ
authors: Choi
authors: 2. Department of Hospital Pathology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
authors: Jinyoung
authors: J
authors: Yoo
mesh_terms: D000368:Aged; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases
keywords: Diffuse large B-cell lymphoma; Epigenetic; Histone deacetylase; Nodal lymphoma; Survival