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Study on the Expression and Clinical Significance of Heparanase and Hypoxia-inducible Factor-2a in Renal Clear Cell Carcinoma on Human

Author: ZouHuaWei
Tutor: QiaoBaoPing
School: Zhengzhou University
Course: Surgery
Keywords: Heparanase Hypoxia-inducible factor - 2a Renal cell carcinoma
CLC: R737.11
Type: Master's thesis
Year: 2009
Downloads: 10
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Abstract


Background and purpose of renal cell cancer (renal cell carcinoma, RCC) is a common solid tumor of the urinary system, the incidence of urinary tract tumors, accounting for adult cancer 2% to 3%, of which 60% to 85% of sporadic clear cell renal cell. Sporadic renal clear cell the early lack typical clinical symptoms, about 30% of patient visits have tumor metastasis. Only surgery and immunotherapy often up to less than the long-term quality survival, there is an urgent need to find a safe and efficient approach. The heparanase (heparanse, Hpa) is a glucuronide endonuclease degradation destroy the integrity of the matrix and basement membrane, and to facilitate a large number of growth factors such as vascular endothelial growth factor release, accelerate the formation of blood vessels, eventually leading to tumor invasion and metastasis. Hypoxia-inducible factor-2α (Hypoxia inducible factor, HIF-2α) is the activity of key transcription factors play only a specific hypoxic conditions mediated angiogenesis six to 70 target genes involved transcription. In tumor angiogenesis, invasion and metastasis of the tumor radiotherapy and chemotherapy tolerance is of great significance. Studies have shown that HIF-2a in renal cell carcinoma expression of tumor invasion, metastasis and prognosis. But for comparison and clinical significance of HIF-2a and Hpa expression in renal cell carcinoma rarely reported. In this study, the detection Hpa, HIF-2a in sporadic renal cell carcinoma in different groups of expression and co-expression, and to explore differences in the expression of Hpa, HIF-2α in the different groups in the distribution of renal cell carcinoma. Clinical treatment and prognosis of theoretical parameters. Method to collect the First Affiliated Hospital of Zhengzhou University, July 2005 to October 2008, 66 patients with pathological surgical specimens confirmed as clear cell renal cell carcinoma, 43 cases were male and 23 female. Aged 25 to 79 years, mean (66 ± 5) years. All patients were not as radiotherapy, chemotherapy; specimens to obtain the informed consent of patients or their families. With lymph node metastasis in 13 cases, 53 cases without lymph node metastasis. Clinical stage based on clinical staging criteria in 2002: Ⅰ 13 cases, 18 cases of Phase II, Phase III 18 cases, Ⅳ of 17 cases. Set Ⅰ, Ⅱ period of the early group, Phase III and IV of the late group. Nuclei of tumor pathology according to Fuhrman grade: G 1 grade 20 cases, the G 2 , and 31, the G 3 level 15 cases. For ease of study, the group is set the G 1 -class well-differentiated group G 2 , the G 3 -level classified as a group, is set to poorly differentiated group. 35 cases of adjacent normal renal tissue (away from the edge of the tumor> 2cm) as control, and confirmed by biopsy. The specimens were fixed in 10% formalin, conventional dehydration embedding, as 4μm serial sections. By immunohistochemistry SP method Hpa, HIF-2α protein expression. Results of statistical analysis using SPSS 13.0 software: the relationship between the HPA, HIF-2a expression in renal cell carcinoma with clinical, pathological indicators with the t test; differences in the experimental group and the control group with x < sup> 2 test and Fisher's exact test. Alpha = 0.05 significance level. Results 1.35 normal renal tissues in Hpa less positive expression of HIF-2a. Hpa membrane or cytoplasmic staining of HIF-2a nucleus staining. 66 cases of renal clear cell carcinoma, the expression of Hpa-positive 28 cases, the positive rate was 42.4%, the expression of HIF-2a positive in 43 cases, the positive rate was 65.2%. Adjacent normal kidney tissue Hpa positive expression of HIF-2a positive expression cases, the differences were statistically significant (P <0.05), compared with the adjacent normal tissue. Lymph node metastasis in 13 patients, the expression of HIF-2a positive 13 cases, no negative expression, the positive rate was 100% (do not rule out the derived factor); lymph node metastasis in 53 patients, the expression of HIF-2a positive 30 cases, negative expression in 23 cases, the positive rate was 56.6%. Between the two groups of HIF-2a expression differences statistically meaningful (x 2 = 7.01, P <0.01). 13 cases of Hpa expression in lymph node metastasis group, the positive rate of 84.6%. Lymph node metastasis group of 53 cases of Hpa-positive expression in 17 cases, negative expression in 36 cases, the positive rate of 32.1%. Lymph node metastasis group Hpa expression was higher in lymph node metastasis group, the difference was statistically significant (X 2 = 11.8, P <0.005). The pathological stage HPA well-differentiated set of positive expression in 7 cases, negative in 13 cases, the positive rate was 35%. Poorly differentiated group of 46 patients, the positive expression in 21 cases, the positive rate was 45.7%. The positive rate of expression of the two groups the difference was not statistically significant (the x 2 = 0.647, P> 0.05). HIF-2a group: well-differentiated set of positive expression in 11 cases, the positive rate was 55%; poorly differentiated group expression in 32 cases, the positive rate of 69.6%. The positive rate of expression of the two groups the difference was not statistically significant (the x 2 = 1.30, P> 0.05). Clinical stage Hpa-positive expression in 10 cases of 31 patients with early renal clear cell carcinoma, negative expression in 21 cases, the positive rate of 32.3%. 35 patients with advanced Hpa expression in 21 cases of negative expression in 14 cases, the positive rate of 60.0%. The Hpa In early and late renal clear cell carcinoma positive expression rate difference was statistically significant (X 2 = 5.23, P <0.05). Expression of HIF-2a positive in 12 cases, 31 cases of early renal clear cell carcinoma with negative expression in 19 cases, the positive rate was 38.7%. 35 patients with advanced set of HIF-2a positive expression in 31 cases, negative expression in 4 cases, the positive rate was 86.6%. HIF-2a in the morning, the positive expression rate of a statistically significant difference in renal clear cell carcinoma of the late group (X 2 = 18.0, P <0.05). 5.Hpa the relationship between the expression of HIF-2a: in renal cell carcinoma Hpa and HIF-2a expression strength of good consistency. Conclusion 1.Hpa, HIF-2a expression and clinical stage renal cell carcinoma significant correlation. In advanced renal clear cell carcinoma Hpa, the expression of HIF-2a higher. Hpa, HIF-2α can be combined expression of the case as one of the parameters in patients with advanced cancer prognosis in clear cell renal cell theory.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Urinary tumors > Kidney,renal pelvis tumor
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