The possible prognostic role of histone deacetylase and transforming growth factor β/Smad signaling in high grade gliomas treated by radio-chemotherapy: a preliminary immunohistochemical study

  • Roberta Sferra | roberta.sferra@univaq.it University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, Italy.
  • Simona Pompili University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, Italy.
  • Claudio Festuccia University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, Italy.
  • Francesco Marampon University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, Italy.
  • Giovanni L. Gravina University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, Italy.
  • Luca Ventura San Salvatore Hospital, Pathology Division, Italy.
  • Ernesto Di Cesare University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, Italy.
  • Sara Cicchinelli University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, Italy.
  • Eugenio Gaudio Sapienza University, Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Italy.
  • Antonella Vetuschi University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, Italy.

Abstract

Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system. Unfortunately, patients affected by this disease have a very poor prognosis, due to high level of invasiveness and resistance to standard therapies. Although the molecular profile of GBM has been extensively investigated, the events responsible for its pathogenesis and progression remain largely unknown. Histone Deacetylases (HDAC) dependent epigenetic modifications and transforming growth factor (TGF)-β/Smad pathway seem to play an important role in GBM tumorigenesis, resistance to common therapies and poor clinical outcome.  The aim of this study was to evaluate the involvement and the possible interaction between these two molecular cascades in the pathogenesis and prognosis of GBM. Immunohistochemistry (IHC) was performed on microdissected GBM samples, collected from 14 patients (6 men and 8 women) ranging in age from 43 to 74 years. The patients were previously divided, on the basis of their overall survival (OS), into two groups: short and long OS. Patients with poor prognosis showed hyperexpression of HDAC4 and HDAC6, an activation of the TGF-β/Smad pathway, with high levels of IL-13, Smad2, PDGF and MMP3 expression, compared to the long survivors. The short OS group exhibits a decrease in Smad 7 expression and also low levels of p21 immunostaining, which represents a common target of the two pathways. The IHC data was confirmed by quantitative analysis and Immunoblotting. Our preliminary results suggest that both HDAC4 and HDAC6 together with the TGF-β/Smad pathway may be involved in progression of GBM and this cross talking could be a useful prognostic marker in this deadly disease.

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Published
2017-05-16
Section
Original Papers
Keywords:
Glioblastoma, histone deacetylases, TGF-β/Smad, radioresistance
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How to Cite
Sferra, R., Pompili, S., Festuccia, C., Marampon, F., Gravina, G. L., Ventura, L., Di Cesare, E., Cicchinelli, S., Gaudio, E., & Vetuschi, A. (2017). The possible prognostic role of histone deacetylase and transforming growth factor β/Smad signaling in high grade gliomas treated by radio-chemotherapy: a preliminary immunohistochemical study. European Journal of Histochemistry, 61(2). https://doi.org/10.4081/ejh.2017.2732

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