Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Eder, M.
The role of hypoxia inducible factor (HIF) in angiogenesis of malignant lung tumours.
[ Diplomarbeit/Master Thesis ] Graz Medical University; 2009. pp.74.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Popper Helmuth
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- Abstract:
- Lung cancer is still the most common malignancy and leading cause of cancer death worldwide. The aim of this study was to identify the role of hypoxia inducible factor 1 alpha (HIF1 alpha) in angiogenesis of malignant lung tumours. We performed a retrospective immunohistochemistry study on tissue microarrays for adenocarcinomas, squamous cell carcinomas, large cell carcinomas, pleomorphic carcinomas, large cell neuroendocrine carcinomas and small cell lung carcinomas. The expression of eleven parameters (factors of hypoxia and angiogenesis) HIF1 a, CAIX, TIE2, VEGFA, VEGFB, VEGFC, VEGFD, VEGFR2, VEGFR3, PDGFRa and PDGFRb was evaluated by light microscopy. Product scores composed of intensity and percentage of stained cells were calculated for statistics. Statistic analyses provided boxplots, Wilcoxons rank sum test comparing expression patterns between NSCLC subentities and SCLC, and Goemans Global Test in order to compare NSCLC subtypes for preferences in activation of the above mentioned factors. Significant differences in activation of signaling pathways between all five NSCLC subtypes do exist. In adenocarcinomas and large cell neuroendocrine carcinomas the expression of VEGFC/VEGFD VEGFR3 signaling was strongest. Large cell carcinomas showed highly activated levels of VEGFA, VEGFD, VEGFR3 and PDGFRa. Pleomorphic carcinomas were characterized by a high expression of all tested parameters except VEGFB and TIE2. Squamous cell carcinomas showed a preference for VEGFC/VEGFD PDGFRb signaling. SCLC followed no typical expression pattern of angiogenesis growth factors and receptors and seem to differ strongly from NSCLC signaling, again providing arguments for their different behavior in contrast to NSCLC. Generally, HIF1 alpha staining reactions were much lower than those for VEGFA/C/D and VEGF receptors expression, except in case of pleomorphic carcinomas, which showed nearly similar staining reactions for HIF1 alpha and the VEGF family. However, our statistics do not provide direct associations between HIF and VEGF signaling. It seems that other proteins besides HIF may be involved in the up-regulation of angiogenesis as well and may play an even more important role.