Clinical Significance of the Immunohistochemical Expression of Histone Deacetylases (HDACs)-2, -4, and -5 in Ovarian Adenocarcinomas

被引:1
作者
Levidou, Georgia [1 ]
Arsenakis, Dimitrios [2 ]
Bolovis, Dimitrios I. [2 ]
Meyer, Roxanne [1 ]
Brucker, Cosima V. M. [2 ]
Papadopoulos, Thomas [1 ]
Theocharis, Stamatios [3 ]
机构
[1] Paracelsus Univ, Med Sch, Dept Pathol, Klinikum Nuremberg, D-90419 Nurnberg, Germany
[2] Paracelsus Univ, Klinikum Nuremberg, Med Sch, Dept Gynecol & Obstet, D-90419 Nurnberg, Germany
[3] Natl & Kapodistrian Univ Athen, Dept Pathol 1, Athens 11527, Greece
关键词
HDAC; ovarial adenocarcinoma; immunohistochemistry; prognosis; TRANSCRIPTION; REPRESSION; PROGNOSIS; HDACS;
D O I
10.3390/biomedicines12050947
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Histone deacetylases (HDACs) are implicated in carcinogenesis, and HDAC inhibitors (HDACis) are explored as a therapeutic tool in several tumors. The aim of this study was to evaluate the clinical significance of HDAC-2, -4, and -5 expression in epithelial ovarian carcinoma (EOC). Methods: HDAC-2, -4, and -5 immunohistochemical expression was examined in 92 EOC tissue specimens and was correlated with clinicopathological characteristics. Results: HDAC-2 was the most frequently (94.4%) expressed isoform, being marginally higher in serous tumors compared with other types (p = 0.08). HDAC-5 was the less frequently expressed (28.1%), being positively associated with HDAC-4. HDAC-4 positivity was associated with lower FIGO-stage (p = 0.045) and T-category (p = 0.043) and the absence of lymph node (p = 0.05) or distant metastasis (p = 0.09) in serous carcinomas. HDAC-2 positivity was correlated with the absence of lymph node metastasis in serous tumors (p = 0.045). On the contrary, HDAC-5 nuclear positivity was correlated with lymph node metastasis in the entire cohort (p = 0.048). HDAC-4 positivity was marginally associated with favorable prognosis in serous carcinomas in univariate survival analysis (p = 0.086), but this correlation was not significant in multivariate analysis. Conclusions: These findings suggest a differential expression among HDAC-2, -4, and -5 in ovarian adenocarcinomas in terms of immunolocalization, positivity rate, and associations with clinicopathological parameters, providing evidence for a potential role in the pathobiology of EOC.
引用
收藏
页数:16
相关论文
共 31 条
[1]  
Ashraf A.Z., 2020, J. Cancer Treat. Diagn, V4, P17, DOI [10.29245/2578-2967/2020/2.1179, DOI 10.29245/2578-2967/2020/2.1179]
[2]   The Sir2 family of protein deacetylases [J].
Blander, G ;
Guarente, L .
ANNUAL REVIEW OF BIOCHEMISTRY, 2004, 73 :417-435
[3]   Histone modifications silence the GATA transcription factor genes in ovarian cancer [J].
Caslini, C. ;
D Capo-Chichi, C. ;
Roland, I. H. ;
Nicolas, E. ;
T Yeung, A. ;
Xu, X-X .
ONCOGENE, 2006, 25 (39) :5446-5461
[4]   Aberrant transforming growth factor β1 signaling and SMAD4 nuclear translocation confer epigenetic repression of ADAM19 in ovarian cancer [J].
Chan, Michael ;
Huang, Yi-Wen ;
Hartman-Frey, Corinna ;
Kuo, Chieh-Ti ;
Deatherage, Daniel ;
Qin, Huaxia ;
Cheng, Alfred S. ;
Yan, Pearlly S. ;
Davuluri, Ramana V. ;
Huang, Tim H. ;
Nephew, Kenneth ;
Lin, Huey-Jen L. .
NEOPLASIA, 2008, 10 (09) :908-U17
[5]   Histone deacetylases (HDACs): characterization of the classical HDAC family [J].
De Ruijter, AJM ;
Van Gennip, AH ;
Caron, HN ;
Kemp, S ;
Van Kuilenburg, ABP .
BIOCHEMICAL JOURNAL, 2003, 370 :737-749
[6]   A multidisciplinary approach remains the best strategy to improve and strengthen the management of ovarian cancer (Review) [J].
Falzone, Luca ;
Scandurra, Giuseppa ;
Lombardo, Valentina ;
Gattuso, Giuseppe ;
Lavoro, Alessandro ;
Distefano, Andrea Benedetto ;
Scibilia, Giuseppe ;
Scollo, Paolo .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2021, 59 (01)
[7]   HDACs, histone deacetylation and gene transcription:: from molecular biology to cancer therapeutics [J].
Gallinari, Paola ;
Di Marco, Stefania ;
Jones, Phillip ;
Pallaoro, Michele ;
Steinkuhler, Christian .
CELL RESEARCH, 2007, 17 (03) :195-211
[8]   Influence of a novel histone deacetylase inhibitor panobinostat (LBH589) on the growth of ovarian cancer [J].
Garrett, Leslie A. ;
Growdon, Whitfield B. ;
Rueda, Bo R. ;
Foster, Rosemary .
JOURNAL OF OVARIAN RESEARCH, 2016, 9
[9]   Histone deacetylase (HDAC)-1,-2,-4 and-6 expression in human pancreatic adenocarcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival [J].
Giaginis, Constantinos ;
Damaskos, Christos ;
Koutsounas, Ioannis ;
Zizi-Serbetzoglou, Adamantia ;
Tsoukalas, Nicolaos ;
Patsouris, Efstratios ;
Kouraklis, Gregorios ;
Theocharis, Stamatios .
BMC GASTROENTEROLOGY, 2015, 15
[10]   Unraveling the Epigenetic Role and Clinical Impact of Histone Deacetylases in Neoplasia [J].
Goutas, Dimitrios ;
Theocharis, Stamatios ;
Tsourouflis, Gerasimos .
DIAGNOSTICS, 2021, 11 (08)