| [Background and objectives]The pathogenesis of renal cell carcinoma is a progression with many steps and phases in which many factors participate in. There exists hypoxian microenvironment in many entity tumors due to structural and functional abnormality of vessel and increased oxygen consumption caused by rapid proliferation of tumor cell in it . Under these circumstances , various cytokines, which can promote growth and metastasis of tumor , are induced to release , therefore, tumor resistance to radiotherapy and chemotherapy is induced . Hypoxia inducible factor-1 (HIF-1) , which generally resides in hypoxian mammal and human cells , has already been identified as one critical protein production directly reacting to hypoxia . Hypoxia inducible factor 1 alpha (HIF-1 α ), not only regulatory subunit but also active one , involving cell metabolism of energy and angiogenesis , is closely associated with formation and development of many kinds of tumors. The expressions of HIF-1 α , microvessel density (MVD) and proliferating cell nuclear antigen (PCNA) were analyzed by immunohistochemical methods to explore the role of HIF-1 α in carcinogenesis and development of renal cell carcinoma.[Materials and methods]66 cases of surgically resected renal cell carcinoma tissues were collected . 40were male , 26 female . 48 were renal clear cell carcinoma , 18 renal granule cell carcinoma. There were lymph nodes metastases in 12 cases , and no lymph nodes metastases in 54 cases. Robson stage I were in 29 cases, stage II in 24 cases, stage III in 12 cases , stage IV in 1 cases ; Thoenes grade 1 renal clear cell carcinoma were in 20 cases, G2 in 19 cases, G3 in 9 cases ; Gi renal granule cell carcinoma were in 8 cases > G2 in 6 cases n G3 in 4 cases . 10 cases of normal renal tissues were regarded as control group . All the tissues were fixed in 10% formalin and embedded in paraffin . 4 micrometers(um) sections were made from representative blocks of each case . Immunohistochemical methods were used to detect the expression of HIF-1 a , CD34 and PCNA .The data were analyzed by software SPSS 10.0. Chi-square test and Spearman analyze were used to compare the difference of HIF-1 a expressions between groups.T test was used to compare the difference of MVD between groups, and Analysis of Variance was applied to compare the difference of PCNAIJ between groups. P<0.05 was considered as level of tests .[Results]l.The positive staining of HIF-1 a was mainly located in nucleus of renal carcinoma cells with the positive rate of 63.6% , whereas the positive expression of HIF-1 a in normal tissues was not found and the difference was significant between them (p<0.05). In Gi,G2,G3 grade renal cell carcinoma , the positive rates were 46.4%, 68. 0% and 92. 3% respectively ( p<0.05). The positive rates of stage I renal carcinoma, stage II renal granule cell carcinoma , stage EH~IV renal carcinoma were 51.7%? 58. 3% and 100% respectively , and significant difference was observed between them (p<0.05) . In the groups with and without lymph nodes metastases, the positive rates were 91.7%, 53.1% respectively, the difference between the two groups was significant (p<0.05).2.The MVD in renal carcinoma tissues was 52.65+6.09 ,whereas in normal renal tissues was 18.50+5.18.A significant difference was observed in two (p<0.05) . The MVD in clear, granule renal carcinoma were 52.90+6.42, 54.22+3.74 respectively ,no significant difference was observed between them . The MVD (61.19+3.37) in group with lymph nodes metastases was significantly higher than the MVD in group without lymph nodes metastasis (51.16+4.79) (p<0.05).3. The MVD(54. 53+5.12) in the HIF-1 a positive expression group of renal granular cell carcinoma was significantly higher than that (48. 58+6.15) in HIF-1 a negative group . There was a positive correlation in them though Spearman analyze (rs=0.523, p<0.05).4. The PCNALI in renal carcinoma tissues was 16.G7±8.78(%) , 2.10±3.60(%) in normal renal tissues , a significant difference was observed in two (p<0.05). The PCNALI in clear , granule renal carcinoma were 15.70+9.90(%), 17.06+4.77(%) respectively.The difference was not significant between them . The PCNALI (23.11+7.51(%)) in group with lymph nodes metastasis was significantly higher than the PCNALI (14.30+7.51(%)) in group without lymph nodes metastasis (p<0.05).5.The PCNALI (17.87+8.39%) was significantly in the HIF-1 a positive expression group of renal granule cell carcinoma higher than that (12.33+5.96%) in HIF-1 a negative group . There was a positive correlation between them by Spearman analyse (rs=0.726, p<0.05).[Conclusions]l.The expressions of HIF-1 a were not found in normal renal tissues , but those were high in renal carcinoma ; the expressions of HIF-1 a are related to pathological types , clinical, pathological grade and lymph node metastasis. It could be a marker of renal carcinoma infiltration evaluation.2. The expressions of HIF-1 a were positively correlative to MVD and the expressions of PCNA in renal cell carcinoma, which indicates that HIF-1 a may increase angiogenesis and proliferation in renal cell carcinoma via regulating the transcription of various target genes including VEGF gene , therefore enhancing progression of renal cell carcinoma . Abiological and genetic therapy ,inhabiting angiogenesis proliferation via targeting HIF-1 a gene , may become an alternativechoice for renal cell carcinoma.
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