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Correlations of hypoxia-inducible factor-1α/hypoxia-inducible factor -2α expression with angiogenesis factors expression and prognosis in non-small cell lung cancer

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Chinese Medical Journal 2011年第1期124卷 11-18页

作者： WU Xian-hua QIAN Cheng YUAN Kai Division of Thoracic Surgery Zhongshan Hospital Fudan University Shanghai 200032 China Division of Thoracic Surgery Changzhou Second People's Hospital Changzhou Jiangsu 213003 China

Background Hypoxia-inducible factor （HIF） may play an important role in the process of tumorigenesis as well as tumor progression. The aim of this study was to compare the expression between HIF-1α and HIF-2α in tumor angiogenesis and the overall impact on patient prognosis in human non-small cell lung cancer （NSCLC）. Methods In the current work we compared the immunohistochemical expression of HIF-1α and HIF-21 in surgical specimens of 140 patients with NSCLC in a tissue microarray study. Relationships between HIF-α expression and clinicopathological or angiogenic factors, including prognosis, were analyzed. Results High HIF-1α and HIF-2α expression was noted in 49/140 （35.0%） and in 64/140 （45.7%） of the cases, respectively. There was no direct correlation between HIF-la and HIF-2α expression. Patients with advanced stage tumors had frequent high expression of HIF-2a （P=0.007）, and we also found a significant correlation between HIF-2α and T or N stage （P=0.030 and 0.043, respectively）. HIF-1α showed a marginal association with T stage （P=0.084）, which showed a higher expression in early stage tumors. A significant correlation （p=0.045） was noticed between HIF-1α and vascular endothelial growth factor （VEGF） expression while the expression levels of thymidine phosphorylase （TP）, cyclooxygenase （COX）-2 and microvessel density （MVD） were significantly higher in high HIF-2a tumors （P=0.020, 0.004 and 0.046, respectively）. In addition, univariate analysis of overall survival demonstrated that HIF-2a expression, but not HIF-la, was related to poor outcome （P=-0.001） and it retained significant in multivariate analysis （P=0.036）. Conclusions Taken together, we conclude that HIF-1α and HIF-2α may differentially regulate the major angiogenic factors in different stages of the tumor process in NSCLC. HIF-2α may play a dominant role in tumor angiogenesis and appears to be of obvious value as a significant prognostic factor in NSCLC.

关键词： non-small cell lung cancer hypoxia-inducible factor-l a hypoxia-inducible factor-2α tissue microarray immunohistochemistry angiogenesis factors prognosis

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Angiogenic markers endoglin and vascular endothelial growth factor in gastroenteropancreatic neuroendocrine tumors

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World Journal of Gastroenterology 2011年第2期17卷 219-225页

作者： Patricia Kuiper Lukas JAC Hawinkels Eveline SM de Jonge-Muller Izk Biemond Cornelis BHW Lamers Hein W Verspaget Department of Gastroenterology and Hepatology Leiden University Medical Centre Department of Molecular Cell Biology and Centre for Biomedical Genetics Leiden University Medical Centre

AIM:To investigate the expression and potential prognostic role of vascular endothelial growth factor(VEGF) and endoglin in gastroenteropancreatic neuroendocrine tumors(GEP-NETs) . METHODS:Microvessel density(MVD) in GEP-NETs was evaluated using endoglin and CD31 *** addition,tissue levels of endoglin and VEGF were determined in homogenates by ELISA. RESULTS:Endoglin was highly expressed on tumor endothelial ***31 MVD in GEP-NETs was significantly higher compared to endoglin MVD(P<0.01) .Two-tofour-fold higher tissue levels of endoglin and VEGF were seen in tumors compared to associated normal tissue. This increased endoglin tissue expression in tumors was significantly related to tumor size(P<0.01) ,presence of metastases(P=0.04) ,and a more advanced tumor stage(P=0.02) ,whereas expression of VEGF was not. CONCLUSION:We suggest that endoglin is a potential marker to indicate and predict metastases,which might be useful in the post-resection therapeutic approach of patients with GEP-NETs.

关键词： Neuroendocrine tumor Carcinoid tumor angiogenesis factors Endoglin Vascular endothelial growth factor

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