Expression of Hypoxia-inducible Factor-1α Is Associated With Tumor Angiogenesis in Gastrointestinal Stromal Tumor
| Autor: | Wan-Tzu Chen, 陳婉姿 |
|---|---|
| Rok vydání: | 2004 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 92 Purpose：Angiogenesis is essential for the growth, invasion, and metastasis of tumor. Vascular endothelial growth factor（VEGF）plays an important role in tumor angiogenesis and in tumor metastasis. Hypoxic-inducible factor-1α（HIF-1α）is reported to transactivate expression of VEGF, which is an important angiogenic factor. The aim of this study was to determine whether VEGF, bcl-2,and p53 expression correlate with HIF-1α expression and microvessel density（MVD）by immunohistochemistry method in benign or malignant gastrointestinal stromal tumor（GIST）and to evaluate the relationship of HIF-1α expression and tumor angiogenesis to distinguish the risk of aggressive behavior in GIST and also to evaluated HIF-1α expression correlate with clinicopathological parameters. Material and method：We collected 62 paraffin-embedded specimens which CD117 positive and histologically compatible as benign or malignant GIST were included in the study. Specimens were divided into 3 groups, including 62 cases of GISTs with low risk（n=26）, intermediate risk（n=15）and high risk（n=21）. These sections were examined immunohistochemically for HIF-1α, VEGF, bcl-2, and p53 expression. Tumor microvessel density（MVD）was determined by immunohistochemistry with anti-CD31 antibody and estimated by averaging the counts from three x200 fields in the area showing the greatest neovascularization. Result：HIF-1α expression was significantly correlated with the expression of VEGF, bcl-2, p53, MVD value, tumor size, and risk of aggressive behavior in GIST（respectively, P=0.002, P＜0.001, P＜0.001, P＜0.001, P=0.004 and P=0.012）and the data suggest that larger GIST with high risk easily become hypoxic, and degradation of HIF-1α is suppressed. Therefore, HIF-1α might serve as a predicted malignant potential marker. Discussion：HIF-1α may play a critical role in hypoxia-induced tumor angiogenesis and tumor progression of GIST through regulation of VEGF. However, tumor growth rate may not always be associated with hypoxic conditions, whereas, HIF-1α expression may be influenced by factors other than hypoxia. Bcl-2, and p53 overexpression was also detected in malignant GIST. The results suggest that the genetic alteration may plays a role in regulating tumor angiogenesis. Immunohistochemical data suggests a close association of the angiogenic process with the expression of apoptosis related proteins, such as p53 and bcl-2. In our study, p53 and bcl-2 overexpression associates with increasing HIF-1αexpression, and leads to increasing VEGF-mediated tumor angiogenesis. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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