| Research background and purposeRenal cell carcinoma (renal cell carcinoma, RCC) is a kind of common urologic tumor. The incidence rate is the second of urinary tract tumor, accounting for about 2%～3% of adult malignancies.While, of which 60 %～85% are the dissemination of clear cell renal cell . No typical early clinical symptoms were found in RCC. Tumor metastasis were found in approximately 30% of patients when they seeked medical treatment. Both surgery and immunotherapy were often not satisfied for the long-term survival of patients. There is an urgent need to find a safe, efficient approach.Heparanase(Hpa)is an acid glucosidase enzyme,and its degradation undermines the integrity of basement membrane matrix. At the same time, it accelerated the releasing of a large number of growth factors such as vascular endothelial growth factor and the formation of blood vessels. Eventually, it leads to tumor invasion and metastasis.Hypoxia-inducible factor-2α(HIF-2α) was the only one of the key transcription factor ,which played a specific activity under the hypoxic conditions. It may be involved in angiogenesis-mediated 60 or 70 kinds of target gene transcription. It played an important role in tumor angiogenesis, tumor invasion and metastasis and radiotherapy and chemotherapy tolerance. Study showed that the expressions of HIF-2α,in renal clear cell carcinoma ,were closely related with tumor invasion, metastasis and prognosis. However, only a few research about comparison of the expression and clinical significance of Hpa, HIF-2αin RCC. In this study, we detected Hpa, HIF-2αamong three groups and their co-expression to explore the clinical significance of the differences .With a view to providing a theoretical parameter for the clinical treatment and estimates prognosis.Methods66 cases of renal clear cell carcinoma were studied , which were confirmed by pathology from surgical resection specimens between July 2005 and October 2008 , in the First Affiliated Hospital of Zhengzhou University. Of which 43 cases were male, while 23 cases were female. The ages were from 25 to 79 years old, on average (66±5) years. None of the patients recerved preoperative radiotherapy and chemotherapy. Specimens were obtained in condition of consents of patients or their families. There were 13 cases with lymph node metastasis, 53 cases without lymph node metastasis. The basis of Clinical stage was according to standard of clinical stage in 2002: I period 13 cases, II period 18 cases, III period 18 cases, IV period 17 cases.We setted stage I, II period as the early group, III,IV period as the late group. Pathological nuclear grade in tumor cells was according to standard of Fuhrman nuclear grade: G1-grade 20 cases, G2 grade 31 cases, G3 grade 15 cases. In order to easying the study, we setted G1-level as the well-differentiated group and setted G2, G3-class as the poorly differentiated group. 35 cases of adjacent normal renal tissue (the edge away from the tumor> 2cm) were done and confirmed by biopsy. Specimens were fixed by 10% formaldehyde, which were dehydryed conventionally embedding for serial sections 4μm. Immunohistochemical SP method was used to examine the expression of heparanase and HIF-2αprotein. The statistical results were analysised by software of SPSS13.0: The t-test , chi-square test and Fisher's exact probabilities were used to process the data.α=0.05 were considered as the significant test level.Results1. Less expression of Hpa and HIF-2αwas detected in 35 cases of normal kidney tissue. The positice expressions of Hpa were cytoplasmic staining, while the nucleus were stained by HIF-2α. In renal clear cell carcinoma specimens, the positive expression rate of Hpa was 42.4%(28/66), while the positive expression rate of HIF-2αwas 65.2%(43/66). In adjacent normal renal tissue, the positive expression of Hpa is 2 cases, HIF-2αexpression in 3 cases. With relatively normal tissue adjacent to cancer, the differences were statistically significant.2. In all of 13 cases of patinds with lymph node metastasis, the positive expression rate of HIF-2a was 100% (could not rule out the possibility). The 53 patinds without lymph node metastasis, the positive expression rate of HIF-2αwas 56.6%(30/53). The positive expressions of HIF-2α,in the two groups ,were statistically differences.In 13 cases patinds with lymph node metastasis, the positive expression rate of Hpa was 84.6%(11/13). In 53 cases without lymph node metastasis, the positive expression rate of Hpa was 32.1%(17/53). The positive expression rate of lymph node metastasis group was higher than which of lymph node metastasis group. The difference was significant.3. Pathological stage In G1 high-level group of Hpa , the positive expression rate was 35%(7/20). While, in 46 cases of poorly differentiated group, the positive expression rate was 45.7%(21/46). There was no significant difference in the positive expression rate of the two groups .In groups of HIF-2α: In high-level group, 11 cases were positive expression and the positive rate was 55%. In poorly differentiated grade, 32 cases were positive expression, while the positive rate was 69.6%. There was no significant difference in the positive expression rate of the two groups .4. Clinical stage In early group of 31 cases of renal clear cell carcinoma, the positive expression rate of Hpa was 32.3%(10/31). In the group of 35 late cases, the positive expression rate of Hpa was 60.0%(14/35). In the early and late group of clear cell renal cell carcinoma, there was statistically significant difference in the positive expression rate of Hpa.In early group of 31 cases of renal clear cell carcinoma, the positive expression rate of HIF-2αwas 38.7%(12/31). In the late group of 35 cases, the positive expression rate of HIF-2αwas 86.6%(31/35), four cases of negative expression. In the early and late group of clear cell renal cell carcinoma, the positive expression rate of HIF-2a was statistically significant difference.5. The expression of Hpa and HIF-2α: In renal clear cell carcinoma, the expression of Hpa and HIF-2αwas good consistency (Kappa=0.615) in intensity.Conclusion1. In renal clear cell carcinoma,there was significantly related to expression of Hpa, HIF-2αand clinical stage.2. In the middle and advanced renal clear cell carcinoma, the positive expression of Hpa and HIF-2αwas higher than that of early. A joint expression of Hpa, HIF-2αcould be used as one prognosis parameter for Rcc. |
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