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Research background and purpose of renal cell cancer (renal cell carcinoma, RCC) is the most common solid tumors of the urinary system, tumor angiogenesis wealth of its features. According to statistics, the incidence of urinary tract tumors, behind the bladder tumor, accounting for about 3% of adult malignancies. The biological characteristics of the invasion and metastasis of malignant tumors, kidney cancer is no exception, about 1/4 of the patients due to the lack of typical clinical symptoms of kidney cancer early, when treatment has been tumor metastasis. The overall efficacy of kidney cancer and are not satisfied, and in-depth understanding of the pathogenesis of kidney cancer and on this basis to explore methods of early diagnosis and treatment is very necessary. Study of kidney cancer invasion and metastasis, the molecular mechanisms that contribute to the design and looking for new ways to further improve kidney cancer prognosis of anti-tumor invasion and metastasis. The occurrence of kidney cancer, the development of a multi-stage, multi-step gradual evolution of the many factors involved. Because the intratumoral vascular structure and function abnormalities as well as the rapid proliferation of tumor cells caused by the tumor cells oxygen consumption increased, many solid tumors have hypoxic microenvironment. Tumor hypoxia can induce the release of a variety of cytokines, but easy to make the tumor cells, thereby promoting tumor growth and metastasis of radiotherapy, chemotherapy tolerance. Recently that hypoxic state, the organization can produce hypoxia-inducible factor (hypoxia inducible factor, HIF). It can regulate a variety of of hypoxia related target gene expression, and that the body can produce a series of hypoxia adaptive response. HIF activity to maintain the energy metabolism of tumor cells to promote angiogenesis, plays an important role in promoting tumor proliferation and metastasis. It is not only overexpressed in the cells of the tumor cells and metastases; can induce abnormal gene expression in tumor tissue, have an important impact on tumor cell growth and apoptosis. Were found in the human body expression of hypoxia-inducible factor currently there are three subtypes of HIF-1 of HIF-2 and HIF-3. α subunit in its functional subunits. HIF-1α exists widely used as a hypoxia-inducible factor, but its low expression levels. HIF-2α expression of the wider organization, there is a significant difference between the amount of expression in different tissues, HIF-3α is a subtype of hypoxia-inducible factor only recently discovered it in heart, skeletal muscle and lung tissue higher expression levels, and lower expression in the liver and kidney tissue. Numerous studies show that HIF-1α expression in a variety of tumors, also highly expressed in renal cell carcinoma, the expression of tumor invasion, metastasis and prognosis. For comparison HIF-2α and HIF-1α expression in renal cell carcinoma and their correlation with tumor angiogenesis compare domestic and foreign but so far has not been reported. The purpose of this study is to detect HIF-1α, HIF-2α and CD34 expression in renal cell carcinoma, and to explore the relationship the HIF and tumor angiogenesis, and HIF-1α, HIF-2α expression differences in renal cell carcinoma. Looking for determining renal cell carcinoma metastasis and estimate prognosis molecular markers, and a new target for anti-cancer therapy. Collected hospital from July 2005 to May 2006, 60 patients with renal cell carcinoma surgical resection specimens, including 41 cases of male and 19 female. Aged 35 to 76 years, with an average age of 61 years. Were not for all specimens preoperative radiotherapy, chemotherapy, specimens by postoperative pathology confirmed 43 cases of renal cell carcinoma, renal granular cell carcinoma 17 cases; lymph node metastasis in 11 cases without lymph node metastasis 49 cases. Tumor stage based on the 1997 International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) staging Ⅰ 31 cases, Ⅱ 17 cases, Ⅲ of nine cases, Ⅳ three cases. 9 cases, tumor nuclear grade based on the 1982 Fuhrman standard, G 1 19 cases of grade, G 2 32 cases of grade G 3 level . Control, and take the 15 cases of adjacent normal renal tissue (away from the edge of the tumor> 5 cm) were pathologically confirmed. Fixed specimens in 10% formalin, the conventional dehydration embedding for 4μm serial sections. Immunohistochemistry SP method was used to detect the expression of HIF-1α, HIF-2α and CD34 protein. Results using SPSS10.0 software statistical analysis, the relationship between HIF-1α, HIF-2α and CD34 expression in renal cell carcinoma with clinicopathological parameters t test; Spearman correlation analysis of the relationship between the various indicators; The differences in the experimental group and the control group by χ 2 test and Fisher's exact test. Α = 0.05 level of inspection. Results showed no positive expression of HIF-1α, HIF-2α 1.15 cases of normal kidney tissue. 60 patients with renal cell carcinoma, HIF-1α positive expression in 37 cases, the positive rate of 61.7%, and 78.3% of the 47 cases, the positive rate of positive expression of HIF-2α. The differences were statistically significant (P <0.01) compared with adjacent normal tissue. 2. Renal cell carcinoma HIF-2α positive expression rate was 78.3%, HIF-1α expression was 61.7%, the difference was statistically significant (χ 2 = 3.97, P <0.05). 3. Lymph node metastasis in 11 cases, HIF-1α positive expression of the eight cases, negative expression of the three cases, the positive rate of 72.7%, lymph node metastasis group (49 cases), HIF-1α, 29 cases of positive expression, negative expression in 20 cases, the positive rate of 59.2% . Between the two groups of HIF-1α expression difference was not statistically significant (the χ 2 = 0.248, P> 0.05). Lymph node metastasis group, 11 cases were positive expression of HIF-2α, the positive rate of 100%. Lymph node metastasis in 26 cases of 49 patients with positive expression of HIF-2α, negative expression in 23 cases, the positive rate of 53.1%, lymph node positive expression rate of HIF-2α metastasis group without metastasis in the lymph nodes, the difference was statistically significant (P = 0.0025). 4. HIF-2α positive group MVD in renal cell carcinoma was 73.3 ± 15.2 53.1 ± 13.4 HIF-2α-negative group MVD, the difference was statistically significant (t = 4.336, P <0.05). HIF-1α-positive group MVD was 70.5 ± 14.8 HIF-1α expression negative group MVD was 66.4 ± 20.1, both compared to the difference was not statistically significant (t = 0.975, P> 0.05). The Spearman rank correlation analysis found that HIF-1α expression and MVD correlation coefficient r the s = 0.181, P> 0.05; HIF-2α expression and MVD correlation coefficient r s = 0.545, P <0.01. We think that there is a positive correlation between the expression of HIF-2α and MVD. Expression of HIF-1α positive 5.43 cases of renal cell carcinoma in 30 cases, negative expression in 13 cases, the positive rate of 69.8%, seven cases of HIF-1α positive expression in 17 cases of renal granular cell carcinoma, negative expression in 10 cases, the positive rate of 41.2 %, HIF-1α in clear cell renal cell carcinoma positive expression rate its positive expression rate of renal granular cell carcinoma, a statistically significant difference (the χ 2 = 4.21, P <0.05) . HIF-2α positive expression in 43 patients with renal cell carcinoma in 38 cases, negative expression of the five cases, the positive rate of 88.3%, 17 cases of renal granular cell carcinoma, the expression of HIF-1α positive in 9 cases, 8 cases with negative expression, the positive rate of 52.9%, HIF-2α in renal cell carcinoma, the positive expression rates of positive expression rate of its renal granular cell carcinoma, a statistically significant difference (χ 2 = 7.04, P <0.05). 6. MVD values ??in renal cell carcinoma 68.9 ± 17.0, 19.3 ± 5.8 in normal kidney tissue, the difference was statistically significant (t = 18.712, P <0.05); clear cell carcinoma, granulosa cell carcinoma were 69.4 ± 15.2,67.7 ± 21.3, the difference was not statistically significant (t = 0.351, P> 0.05); lymph node metastasis was 85.1 ± 17.1, lymph node metastasis group and 65.3 ± 14.8, the difference was statistically significant (t = 3.913, P <0.05). 7. HIF-1α, HIF-2α expression with clinical stage, grade Spearman correlation analysis showed that: HIF-1α expression with tumor stage, grade (r s were 0.104, 0.172, P> 0.05). HIF-2α expression and tumor stage, grading (r s were 0.253,0.223, P> 0.05). Conclusion 1. HIF-1α, HIF-2α in renal cell carcinoma were expressed, and the expression of HIF-2α than HIF-1α broader. 2. HIF-2α expression correlation with MVD, tumor angiogenesis regulatory factor, HIF-2α expression has strong tumor invasion and metastasis. 3. HIF-1α, HIF-2α expression with tumor clinical grading, staging no significant correlation.
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