HIF-1α、VEGF在视网膜母细胞瘤中的表达及意义

Expression and clinical implication of hypoxia-inducible factor-1α and vascular endothelial growth factor in retinoblastoma

目的探讨缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)在视网膜母细胞瘤(RB)组织中表达情况及其在肿瘤血管形成、浸润及转移等生物学行为中作用。方法应用免疫组织化学方法检测RB组织中HIF-1α蛋白、VEGF蛋白的表达情况,并探讨其表达与肿瘤的分级的相关性及HIF-1α和VEGF两者的相关性。结果HIF-1α、VEGF蛋白在RB中呈高表达,HIF-1α阳性细胞为肿瘤细胞核染色、部分胞浆染色,VEGF阳性细胞为肿瘤细胞胞浆染色,HIF-1α、VEGF表达在不同临床分期间差异有统计学意义(P<0.05),且其表达和临床分期密切相关(P<0.05);HIF-1α、VEGF二者表达存在正相关(rs=0.946,P<0.01)。结论HIF-1α及VEGF的高表达与RB的临床分期呈正相关,在RB新生血管形成、肿瘤的浸润、转移中可能发挥重要作用。

Objective The invasion and metastasis of tumor cells depend on the growth of new blood vessels, and tumor neovascularization was regulated by a lots of factors. This study aimed to investigate the expression of hypoxia-indueible factor-1α （HIF -1α） and vascular endothelial growth factor（VECF） in retinoblastoma and explore the correlation of HIF-1α and VEGF with tumor invasion and metastasis and analyze their relationship with clinicopatholngy characters and determine their effect on angiogenesis. Methods Forty-six retinoblasloma specimens with different clinical stages were collected in Affiliated Second Hospital of Nanchang University. The specimens received neither radiotherapy nor chemotherapy. The retinal tissue near the tumor was as control, Immunohistochemistry was used to detect the expression of HIF-1α protein and VEGF protein in retinoblastoma. The relationship between expression of HIF-1α and VEGF and stage of tumor was analyzed. Results The HIF-1α and VEGF were highly expressed in the ischemia or necrosis area of retinoblastoma. Expression of HIF-1α was mainly in cell nuclear and partly in cytoplasm, and VEGF was mainly expressed in cytoplasm of tumor cells. The expression of HIF-1α and VEGF was gradually increased with the rising of tumor stage（ P 〈 0.05 ） and showed significant correlation between expression of HIF-1α and VEGF with tumor stage（ r = 0. 943,P 〈 0.01 ）. HIF-1α exepression was also possitively related to VEGF level in retinoblastoma （r = 0. 946, P 〈 0.01 ）. Conclusion HIF-1α and VEGF were over-expressed in retinoblastoma cells, and the expressions were related to clinical staging, invasion and metastasis of tumor cells. The expression of HIF-1αand VEGF was one of the predictors for the biological behaviors of retinoblastoma. HIF-1αand VEGF may play an important role in angiogenesis and tumor progression in retinoblastoma.