Expression And Clinical Significance Of Hypoxia-Inducible Factor-1α In Clear Cell Renal Cell Carcinoma

Objective and Background:Hypoxia inducible factor-1α(HIF-1α) is a kind of transcription factor generally residing in mammalian tissues. when occupying hypoxia condition. HIF-1, which is the core regulatory factor in charge of vascularization in hypoxia condition, effects the gene regulation and transcription. HIF-1 consists of alpha subunit (HIF-1α) and beta subunit (HIF-1β). HIF-1βis a structional subunit and its expression level in cells is stable. HIF-1αis a functional subunit and not detectable in physiological condition. The level of HIF-1αin cells heightens and takes effect on some inducted conditions. In the tumorigenesis and process of growth, the changes of oncogenes or anti-oncogenes could activate the gene HIF-1. HIF-1α, which was discovered in 1992 from cellular nucleus extractive of oxygen-poor cells by Semenza, is a critical regulatory proteim of cellular response to hypoxia and extensively reside in mamma and human being cells in anoxia condition. HIF-1αis becoming a new hot spot of oncology study recently, it's overexpressed in many tumors and associated with theit biologic behavior such as invasion, metastasis and poor patient prognosis. To study the expression of hypoxia inducible factor-1α(HIF-1α) in renal cell carcinoma (RCC).Materials and Methods:This study included 50 cases of patients, from December,2006 to October,2007, who admitted in the General Hospital of Tianjin Medical University for the treatment of RCC. There are 28 male and 22 female. The median age was 58.2 (range 41-78). The clinical stage was assigned according to the 2002 AJCC TNM system:16 patients of stagingⅠ,19 patients of stagingⅡ,11 patients of stagingⅢand 4 patients of stagingⅣ. For pathologic grading:18 patiens of GradeⅠ,23 patients of GradeⅡand 9 patients of GradeⅢ. None of them had received chemotherapy or radiotherapy before operations.10 specimens of normal renal tissues were acquired as control. Immunohistochemical staining for HIF-1αwas carried out and SPSS 16.0 for windows was used to evaluate the association between HIF-1αexpression and development, progress, clinico-pathologic parameters. Results:1. The positive rate of HIF-la expression in renal cell carcinoma was 62%. While the positive rate of HIF-1αexpression in normal renal tissue was 0%. HIF-1αexpression was significant differential between RCC and normal renal tissues (χ2=12.828,P<0.01).2. The intensive expression of HIF-1αwas related to TNM stage of RCC. The positive rate of HIF-1αexpression at each TNM stage in RCC was 43.8%,57.9％,81.8％,100.0%. HIF-1αexpression was significant differential between early RCC and advanced RCC (χ2=5.534, P<0.05).3. The intensive expression of HIF-la was related to tumor histological classification of RCC. The positive rate of HIF-la expression at each tumor histological classification in RCC was 38.9％,69.6%,88.9%. HIF-1αexpression was significant differential in each tumor histological classification of RCC (χ2=7.401, P<0.05).Conclusion:1. HIF-1αwas highly expressed in RCC tissues which may predict it can play an very important role in the occurrence and development in RCC.2. The expression of HIF-1αin renal cell carcinioma was related to TNM stage. The more expression of HIF-1α, the more TNM stage.3. The expression of HIF-1αin renal cell carcinioma was related to tumor histological classification. The more expression of HIF-1α, the more tumor histological classification.4. It may serve as an important indicators to evaluate the biological behaviors of RCC and become a new research direction for anti-tumor therapy.