Expression Of Hypoxia Inducible Factor-1α And Vascular Endothelial Growth Factor In Human Renal Cell Carcinoma

Background and Objective Renal carcinoma is also called renal cell carcinoma(RCC)or adenocarcinoma of kidney, which is the most frequent substantive tumor of kidney. Invasion and metastasis is two important biologic characters of malignant tumor,it's the same for renal cell carcinoma.Accoring to lacking of typical clinical symptom,about 1/4-1/3 of the patients with renal cell carcinoma had metastasis when they visited doctor, it may be hematogenous metastasis or lymphatic metastasis. Studying the molecular mechanism about invasion and metastasis of renal cell carcinoma,is not only helpful to offer valuable molecule markers for clinical judgement prognosis,but also helpful to design and look for a new way to resist invasion and metastasis and to improve the prognosis.Hypoxia-inducible factor 1 alpha (HIF-1α) ,which was discovered in 1992 from cellular nucleus extractive of oxygen-poor cells by Semenza, is a critical regulatory protein of cellular response to hypoxia and extensively reside in mamma and human being cells in anoxia condition. HIF-1 a is becoming a new hot spot of oncology study recently, it's overexpressed in many tumors and associated with their biologic behavior such as invasion,metastasis and poor patient prognosis.VEGF(vascular endothelial growth factor)is the most potent and critical inducer of angiogenesis.It's essential for vascularization, specially acting at vascularendothelial cell and inducing cellproliferation,transfer and cavitation. VEGF facilitate tumor's growth ,invasion and metastasis by stimulating blood vessel formation .HIF-la is an upstream transcription factor of VEGF gene.Resent studies have demonstrated that overexpression of VEGF, HIF-la are positively associated with invasion,metastasis and poor patient prognosis in many tumors.Therefore, VEGF> HIF-la may become the important target of anticancer therapy ,which has become the focus of clinical and experimental study, and several experimental studies have given promising results. But to our knowledge,until now,only few data exist on the correlation of VEGF and HIF-la protein expression with invasion,metastasis and patient prognosis in RCC.The aim of this study was to investigate the expression of HIF-la and VEGF in RCC and their relationship, as well as their prognostic impact in patients with RCC.Materials and Methods 42 cases with RCC were selected who had performed operation in our hospital between 2003.1 to 2004.12,of which 18 cases were confirmed accompany with metastasis,and others weren'tAU the patients didn't received any form of radiaotherapy,chemotherapy and immunotherapy.The expression of HIF-la and VEGF were tested by SABC immunohistochemical methods in those 42 RCC tissue samples and 10 normal kidney tissue that apart from tumor at least 5 cm. All statistical analyses were carried out with SPSS 10.0 software,the categorized data were analyzed with X2 test or McNeal test when appropriate. P<0.05 was considered statistically significant.Results HIF-la protein expression was brown granular,and mainly localized in nucleus of tumor cells and minor staining was also detected in cytoplasm. VEGF protein expression was brown stain and mainly localized in cytoplasm and cell membrane. The positive rate of HIF-la staining was 57.1% in patients with RCC, and was no expression in tissue around the tumor and normal tissue, the positive rate ofVEGF was 61.9%, and there was a significant difference in VEGF expression between carcinoma tissues and control tissues, P<0.05; The expression level of HIF-la and VEGF was significantly higher in metastatic RCC than that in no metastatic RCC, P<0.01; There was no significant correlation between the positive rate of HIF-la and VEGF staining and the age and gender of patients, the size and histological grade of RCC; HIF-la was significantly correlated with VEGF expression (Kappa=0.41,P<0.01).Conclusion HIF-la and VEGF protein was overexpressed in RCC,and their overexpression is significantly associated with metastasis. VEGF protein expression is positively associated with HIF-la expression. HIF-la and VEGF protein expression were not associated with the age and gender of patients, the size and histological grade of RCC. HIF-la is one of important regulator of VEGFo Immunohistochemical staining for HIF-la and VEGF may be an important indicator in evaluating the biological behavior of RCC such as invasion.metastasis and prognosis of RCC.