Histone deacetylase (HDAC)-1, -2, -4 and -6 expression in human pancreatic adenocarcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival.
BACKGROUND
Histone deacetylases (HDACs) have been associated with malignant tumor development and progression in humans. HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents in clinical trials. The present study aimed to evaluate the clinical significance of HDAC-1, -2, -4 and -6 protein expression in pancreatic adenocarcinoma.


METHODS
HDAC-1, -2, -4 and -6 protein expression was assessed immunohistochemically on 70 pancreatic adenocarcinoma tissue specimens and was statistically analyzed with clinicopathological characteristics and patients' survival.


RESULTS
Enhanced HDAC-1 expression was significantly associated with increased tumor proliferative capacity (p = 0.0238) and borderline with the absence of lymph node metastases (p = 0.0632). Elevated HDAC-4 expression was significantly associated with the absence of organ metastases (p = 0.0453) and borderline with the absence of lymph node metastases (p = 0.0571) and tumor proliferative capacity (p = 0.0576). Enhanced HDAC-6 expression was significantly associated with earlier histopathological stage (p = 0.0115) and borderline with smaller tumor size (p = 0.0864). Pancreatic adenocarcinoma patients with enhanced HDAC-1 and -6 expression showed significantly longer survival times compared to those with low expression (p = 0.0022 and p = 0.0113, respectively), while a borderline association concerning HDAC-2 expression was noted (p = 0.0634).


CONCLUSIONS
The present study suggested that HDACs may be implicated in pancreatic malignant disease progression, being considered of clinical utility with potential use as therapeutic targets.
First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. cgiaginis@aegean.gr.|Department of Food Science and Nutrition, School of Environment, University of the Aegean, Mitropoliti Ioakeim 2, 81400, Myrina, Limnos, Greece. cgiaginis@aegean.gr.
Constantinos
C
Giaginis
Second Department of Propedeutic Surgery, Medical School, University of Athens, Athens, Greece.
Christos
C
Damaskos
First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Ioannis
I
Koutsounas
Department of Pathology, Tzaneio General Hospital, Piraeus, Greece.
Adamantia
A
Zizi-Serbetzoglou
First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Nicolaos
N
Tsoukalas
First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Efstratios
E
Patsouris
Second Department of Propedeutic Surgery, Medical School, University of Athens, Athens, Greece.
Gregorios
G
Kouraklis
First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Stamatios
S
Theocharis
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D056284:Histone Deacetylase 1 / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000378:metabolism; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012097:Repressor Proteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D012097:Repressor Proteins; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human; C400300:HDAC4 protein, human; C433811:HDAC6 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases