Histone deacetylase (HDAC)-1, -2, -4 and -6 expression in human pancreatic adenocarcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival.

Constantinos Giaginis,Efstratios Patsouris,Adamantia Zizi-Serbetzoglou,Stamatios Theocharis,Gregorios Kouraklis,Christos Damaskos,Nicolaos Tsoukalas,Ioannis Koutsounas

doi:10.1186/s12876-015-0379-y

Abstract

BackgroundHistone 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.MethodsHDAC-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.ResultsEnhanced 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).ConclusionsThe present study suggested that HDACs may be implicated in pancreatic malignant disease progression, being considered of clinical utility with potential use as therapeutic targets.

Highlights

Histone deacetylases (HDACs) have been associated with malignant tumor development and progression in humans
We aimed to evaluate the association of HDAC-1, −2, −4 and −6 expression with clinicopathological characteristics, tumor proliferative capacity and patients’ survival
High HDAC-1 expression was significantly associated with increased tumor proliferative capacity (Table 1, p = 0.0238)

Summary

Introduction

Histone deacetylases (HDACs) have been associated with malignant tumor development and progression in humans. Several HDAC inhibitors (HDACIs) have been shown to induce cell cycle growth arrest in both normal and transformed cells and activate the extrinsic and intrinsic pathways of apoptosis [6, 7] Both in vitro and in vivo data and ongoing clinical trials have recently revealed that HDACIs could be used against different solid tumors and hematological malignancies, consisting one of the most promising classes of new anticancer agents [8,9,10,11,12,13]. There is a strong demand for novel specific markers to be explored in respect to pancreatic adenocarcinoma patients’ management and prognosis Chemotherapy, such as treatment with 5-fluorouracil or gemcitabine, is not potentially capable of contributing to significant survival benefit according to the available literature data, their combination is associated with a small survival advantage of about 4 to 8 weeks [16]. The establishment of alternative therapeutic approaches for the treatment of pancreatic cancer remains a great challenge

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Conclusion