Z Gastroenterol 2015; 53 - P27
DOI: 10.1055/s-0035-1551715

Eukaryotic Translation Initiation Factors in Gastroenteropancreatic Neuroendocrine Tumors – A TMA based Study

E Smolle 1, 2, B Sipos 3, P Kump 4, M Thalhammer 5, R Lipp 6, J Haybaeck 2
  • 1University Clinic of Internal Medicine, Department of Angiology, Medical University of Graz, Graz, Austria
  • 2Institute of Pathology, Medical University of Graz, Graz, Austria
  • 3Institute of Pathology and Neuropathology, University Clinic of Tübingen, Tübingen, Germany, Tübingen, Germany
  • 4University Clinic of Internal Medicine, Department of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
  • 5University Clinic of Surgery, Department of General Surgery, Medical University of Graz, Graz, Austria
  • 6University Clinic of Radiology, Department of Nuclear Medicine, Medical University of Graz, Graz, Austria

Eukaryotic translation initiation factors (eIFs) are mediators of start codon recognition in eukaryotes. If activated aberrantly, they might alter cell growth and proliferation, and thus contribute to carcinogenesis.

In the course of the neuroendocrine tumor (NET)-study project at the Medical University of Graz, we have analyzed various eIF subunits in gastroenteropancreatic (GEP)-NETs in a tissue microarray (TMA)-based immunohistochemical study. To the best of our knowledge, not much is yet known about eIFs in NETs in literature, and thus we aimed to gain knowledge about their expression patterns.

We have investigated several eIF subunits in NET- and neuroendocrine carcinoma (NEC)-samples by analyzing the cytoplasmic expression intensity (score 0, 1+, 2+ or 3+), and the density of cells featuring a positive expression (%). As controls, we have analyzed eIFs in the corresponding normal tissues (e.g. normal exocrine or endocrine pancreatic tissue).

Furthermore we correlate the patients' prognosis, e.g. time-to-relapse and overall-survival, with eIF expression levels. Thereby we aim to assess whether eIFs are useful as disease biomarkers.

Our analysis shows that eIFs are obvilously de-regulated in NETs and NECs, as compared to healthy controls. Interestingly, some eIF subunits seem to be up-regulated in tumor tissue, whilst others are down-regulated in tumors, compared to the normal tissue samples.

As conclusion, eIFs display altered expression patterns in NETs and NECs. Thus most likely differential expression of eIFs in NETs influences NET- and NEC-tumorigenesis.

In future eIFs may be potentially useful as disease biomarkers, and they might serve as therapeutic targets.

Acknowledgement:

To Professor Aurel Perren, MD and Annika Blank, MD (Institute of Pathology, University of Bern, Switzerland) for providing NET and NEC tissue samples for our analysis.