Expression Level Of VEGFR-2 And HIF-1α As Prognostic Predictors In Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib

Objective To observe the expression of VEGFR-2 and HIF-1α in tissues of renal cell carcinoma(RCC) and corresponding adjacent kidney tissues, and to investigate the expression of VEGFR-2 and HIF-1α with clinicopathological features such as age, gender, karnofsky performance status, pathologic T stage, histological type, pathological grade, metastatic organ, bone metastasis and so on of RCC. At the same time, to investigate the expression levels of the two molecular markers and clinicopathological features in radical nephrectomy specimens from patients with metastatic renal cell carcinoma(m RCC) treated with sunitinib in order to identify factors predicting susceptibility to this agent.Material and Method A total of 48 patients from department of urology, second hospital of Tianjin medical university, Tianjin institute of urology with RCC undergoing nephrectomy and sunitinib therapy, with accession from August 2008 to October 2013, were included in this study. The median age was 59 years with arrange of 42~73 years. 29 males and 11 females.VEGFR-2 and HIF-1α were detected by immunohistochemistry. The immunohistochemical staining was assessed without knowledge of the patient’s clinicopathological characteristics by two senior pathology doctor through double blind method. Collect the clinicopathological data to investigate the expression of VEGFR-2 and HIF-1α with clinicopathological features and the relationship between the expression levels of the two molecular markers and clinicopathological features and sunitinib efficacy. All the data were analyzed by SPSS 17.0 medical statistics software. The statiscal significance was defined as P<0. 05.The result 1. Expression of VEGFR-2 and HIF-1α in RCC tissues The overexpression ratios of VEGFR-2 in adjacent kidney tissues of carcinoma and renal cell carcinoma were 20.0% and 72.5% respectively. There was significant difference after c2 test(P<0.001). The positively expression ratios of HIF-1α in adjacent kidney tissues of carcinoma and in renal cell carcinoma were 20.0% and 62.5% respectively,showing significant difference(P<0.001) 2. The correlation between expression of HIF-1α and VEGFR-2 in RCC.There was positive significant correlation between HIF-1α and VEGFR-2 in renal cell carcinoma.(P<0.01).3. The relationship between the expression of HIF-1α and VEGFR-2 and characteristics of clinical pathology in RCC.There was no significant correlation between the expression of HIF-1α and VEGFR-2 and age, gender, Karnofsky performance status, metastatic organ, bone metastasis, histological type of patients and so on. But they were positive correlation between the expression of HIF-1α and VEGFR-2 and pathologic T stage, pathological grade(P<0.05).The positive expression ratio of HIF-1α in CCRCC is 81.3%, compared with The positive expression ratio of other histological types is 37.5%, the difference was statistically significant(P <0.05),While VEGFR-2 expression differences between CCRCC and other histological types of RCC was not statistically significant(P> 0.05).4. the relationship between sunitinib efficacy and the expression of VEGFR-2 and HIF-1α and clinicopathological features.we analyzed the relationship between sunitinib efficacy and the expression of VEGFR-2 and HIF-1α and clinicopathological features. The results showed that There was no significant correlation between sunitinib efficacy and expression of HIF-1α and age, gender, Karnofsky performance status, metastatic organ, bone metastasis, histological type of patients, pathologic T stage, pathological grade and so on(P>0.05), While they were positive correlation between the expression of VEGFR-2 and sunitinib efficacy(P<0.05).Conclusion 1. The level of HIF-1α and VEGFR-2 in the tumor tissues is noticeably higher than that in the adjacent kidney tissues. they were positive correlation between the expression of HIF-1α and VEGFR-2 and pathologic T stage,pathological grade, the level of HIF-1α in CCRCC tissues is noticeably higher than other histological types. This shows that HIF-1α and VEGFR-2 plays an important role in the development and progression of renal cell carcinoma, and may promote tumor invasion and metastasis. Therefore, detecting the expression of HIF-1α and VEGF-2 in patients with renal cell carcinoma can contribute to the diagnosis of renal cell carcinoma, and that they can provide the basis for the next treatment and are great valuable biological markers of diagnosis, treatment and prognosis of RCC.2. There was positive significant correlation between HIF-1α and VEGFR-2 in renal cell carcinoma. Thus, HIF-1α and VEGFR-2 has some relevance in the process of the development and progression of RCC.3. There was no significant correlation between sunitinib efficacy and expression of HIF-1α and age,gender,Karnofsky performance status, metastatic organ, bone metastasis, histological type of patients, pathologic T stage, pathological grade and so on, while they were positive correlation between the expression of VEGFR-2 and sunitinib efficacy, so VEGFR-2 may become the predictor of sunitinib treatment.