Expression Of Hif-1α, COX-2 In Renal Cell Carcinoma And Its Correlation With Tumor Angiogenesis

Objective:Renal cell carcinoma(RCC) is one of urology hackneyed malignant tumor. The incidence rate of it has a ascending trend. The biological behaviour of renal carcinoma is very complicated and it is insensitive to radiotherapy and chemotherapy. Nowdays, we are major to use the immunotherapy to the patients of postsurgery and transitivity . But the side effect of that treatment is comparatively large,not all patients can suffer it. Owing to the therapies are not ideal and localized, we need to investigate renal carcinogenesis mechanism and find a new effective treatment to renal cell carcinoma.HIF-1 is a transcription factor which is existing in mammal tissue . In an erobic cendition, it educes transcription and gene regulation effect. It is the cores regulating factor which control blood vessels fruiting.HIF-1αis the function subunit of HIF-1, the Expression of HIF-1αis step-up in many tumor cell.It correlated with tumor biological behaviour and tumor vessel and became a hot spot in tumor research for the past few years. COX-2 can decompose arachidonic acid, it is an important rate-limiting enzyme in endogenous prostaglandin formation process. The study with the correlations between HIF-1αexpression and COX-2 expression in renal cell carcinoma, make for to reveal the mechanism of action with two factors in renal cell carcinoma developing. There is few study with the correlations between the expression of HIF-1αin our country and the correlations between COX-2 and HIF-1αis not clear. There is few study with the correlations between two factors and microvascular density of tumor,too. My research use the methods of immunohistochemisty, to detect 51 specimen of renal cell carcinoma and 21 normo-nephridial tissue .The purpose is to approach the correlations between HIF-1αexpression and COX-2 expression in renal cell carcinoma, to offer a new thread and target point in clinical therapy.Methods:51 specimens of renal cell carcinom and 21 specimens of normal renal tissues were selected from march 2010 to october 2010,men 31 cases,women 20 cases,left side 27 cases,right side 24 cases, age:20-80 years old, average 57.3 years old.All cases have no therapeutics before surgery. There are clear cell carcinoma 41 cases,corpora mammillaria carcinoma 2 cases, chromophobe carcinoma 2 cases,other kind 2 cases.Clinical stage(grouping by Robson methods),Ⅰ8 cases,Ⅱ27 cases,Ⅲ12 cases,Ⅳ4 cases.Pathology grade(grouping by Fuhrman methods),G1 11 cases,G2 21 cases,G3 15 cases,G4 4 cases. 14 specimens have lymphatic metastasis.The expression of HIF-lα,COX-2,VEGF,CD34 were examined by immunohistochemical method(two stage method). We investigated the changes of HIF-lα, COX-2, VEGF and CD34 expression in renal cell carcinom group and control group , and the correlation of its' expression with MVD and clinicopathologic features was also explored. All statistical analyses were carried out with SPSS 13.0 and P<0.05 was considered statistically significant.Results:1 The expression of HIF-lαin RCC is significantly higher than that in normal nephridial tissue. The positive rate of HIF-lαexpression in RCC was 54.9%.While the positive rate of HIF-1αexpression in normal renal tissue was 0%.There were statistic differences between the two(X~2=18.866, P<0. 05). The expression of COX-2 in RCC significantly higher than that in normal nephridial tissue. The positive expression rates were 74.5% and 14.3%. There were statistic differences between the two(X~2 = 22.005, P<0.05).The expression of VEGF in RCC significantly higher than that in normal nephridial tissue. The positive expression rates were 80.4% and 23.8%. There were statistic differences between the two(X~2=20.642, P<0. 05).2 The expression of HIF-1α,COX-2,VEGF were related to tumor histological classification of RCC. The positive rate of HIF-lαexpression in each tumor histological classification of RCC were 27.3%,42.9%,84.2%. There were statistic differences between those classification (X~2=11.656, P<0. 05). There were statistic differences between G1- G2 and G3-G4 (X~2=10.506, P<0. 05) .The positive rate of COX-2 expression in each tumor histological classification of RCC were 45.5%,76.2%,94.7%.There were statistic differences between those classification (X~2=12.552,P<0. 05). There were statistic differences between G1- G2 and G3-G4 (X~2=6.523, P<0. 05) .The positive rate of VEGF expression in each tumor histological classification of RCC were 36.4%,90.5%,94.7%. There were statistic differences between those classifications(X~2=17.362,P<0. 05).There were statistic differences between G1- G2 and G3-G4 (X~2=3.953, P<0. 05) .3 The intensive expression of HIF-1α,COX-2 was related to clinical stage of RCC. The positive rate of HIF-lαexpression at each stage in RCC was 25.0%, 44.4%, 87.5%. There were statistic differences between those stages(X~2=10.948, P<0. 05).There were statistic differences betweenⅠ-ⅡandⅢ-Ⅳ(X~2=10.006, P<0. 05). The positive rate of COX-2 expression at each clinical stage in RCC was 37.5%,74.1%,93.8%. There were statistic differences between those stages(X~2=8.891,P<0. 05).There were statistic differences betweenⅠ-ⅡandⅢ-Ⅳ(X~2=4.544, P<0. 05).The positive rate of VEGF expression at each clinical stage in RCC was 25.0%, 88.9%,93.8%. There were statistic differences between those stages(X~2=18.620, P<0. 05). There were not statistic differences betweenⅠ-ⅡandⅢ-Ⅳ(X~2=2.639, P>0. 05).4 The intensive expression of HIF-1αand COX-2 was related to lymphatic metastasis of RCC. The positive rate of HIF-1αexpression in sufferers have lymphatic metastasis of RCC was 78.6%,while the positive rate of HIF-1αexpression in sufferers didn't have lymphatic metastasis of RCC was 45.9%.There were statistic differences between the two( X~2=4.366,P<0. 05). The positive rate of COX-2 expression in sufferers have lymphatic metastasis of RCC was 100%,while the positive rate of COX-2 expression in sufferers didn't have lymphatic metastasis of RCC was 64.9%.There were statistic differences between the two( X~2=6.602,P<0. 05). The positive rate of VEGF expression in sufferers have lymphatic metastasis of RCC was 85.7%,while the positive rate of VEGF expression in sufferers didn't have lymphatic metastasis of RCC was 78.4%. There weren't statistic differences between the two( X~2=0.347,P>0. 05),we can not believe positive expression of VEGF was related to lymphatic metastasis of RCC.5 The level of MVD in RCC was 55.69±10.73,while in normal renal tissue was 19.98±6.59.There were statistic differences between the two (t =8.781,P<0.05).The level of MVD at each clinical stage in RCC were 42.22±4.11,57.87±6.77,65.21±7.53.There were statistic differences between them(F=7.633,P<0.05).The level of MVD in each tumor histological classification of RCC were 44.31±5.41,59.21±7.98,68.67±9.12. There were statistic differences between them(F=7.572,P<0.05). The level of MVD in sufferers have lymphatic metastasis of RCC were higher than didn't have lymphatic metastasis(t=4.793,P<0.05 ). The levels of MVD in which HIF-1α, COX-2, VEGF protein expression of positive expression were higher than negative expression. There were statistic differences between them (P<0.05).6 Correlation analysis showed that, HIF-1αprotein expression and COX-2, VEGF expression was positively correlated (P<0.05), COX-2 protein expression and HIF-1α, VEGF expression was positively correlated (P<0.05), HIF-1αand COX-2 co-expression and VEGF protein expression was positively correlated (P<0.05). The levels of MVD in which HIF-1αand COX-2 co-expression were higher than negative expression, there were statistic differences between them(P<0.05).Conclusion:1 The extremely high expression of HIF-lα, COX-2,in RCC was related with clinical and pathological staging, lymph node metastasis,tumor angiogenesis;2 HIF-lα, COX-2 may play an important role in promoting tumor angiogenesis by inducing VEGF expression;3 The expression of HIF-lαand COX-2 was positive correlated, they may play a synergistic role in the process in promoting tumor angiogenesis;4 HIF-lαand COX-2 can be new target points in biotherapy of RCC. They also can be markers reflecting the malignancy of tumor.