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The Clinical Significance And Relationships Between Protein Expressions Of Survivin And PTEN In Renal Cell Carcinoma

Posted on:2008-06-29Degree:MasterType:Thesis
Country:ChinaCandidate:Z L XuFull Text:PDF
GTID:2144360215988949Subject:Surgery
Abstract/Summary:PDF Full Text Request
Disorder of cell cycles and misbalance of proliferation and apoptosis give contribution to the carcinogenesis; lose control of cell division is another characteristics. It's widely recognized that oncogenesis of kidney carcinoma is a multigene, multistage process. A lot of reports have showed that activation of oncogenes and inactivation of tumor suppressor genes are involved in renal carcinoma. Survivin, a member of the inhibitor of apoptosis(IAP)family of proteins, is widely expressed in transformed cell lines and in different primary cancer cells. It is not expressed in many non-malignant adult tissues, but is essential for fetal development. The expression of Survivin gene directly relates to the histological classification of carcinoma, its relapse,metastasis, and growth index and inversely relates to apoptotic index.PTEN is a tumor suppressor gene with phosphates activity, has complexful functions including participating in the embryonic growth,apoptosis and G1 phase cell block, inhibiting the migration and adherence. In the present study, we detected the expression of Survivin and PTEN and cell apoptosis in RCC and normal renal tissue by immunohistochemical method, analyzing their correlation, to try to explore the role of Survivin and PTEN in renal carcinogenesis, hoping to provide the new way to the clinical diagnosis and therapy of RCC.Methods: The expression of Survivin and PTEN, was examined by immunohistochemistry S-P method in 20 cases of Para carcinoma, 5 cases of normal renal tissues and 40 of renal cell carcinoma(26 men and 14 women, mean age 53.1 years, range from 23 to 74 years).Cell type of RCC: clear cell type 27 cases, granular cell type 6 cases, mixed-cell type 7 cases. According to Robson staging: stage I 11 cases, stage II 14cases, stage III 10 cases and stageâ…£5 cases.According to Fuhrman grading: grade I 9 cases,grade II 24 cases and grade III 7 cases. Results were compared with clinical pathologic parameters, lymphatic metastasis, and Survivin, PTEN protein expression which were evaluated by immunohistochemical methods, too.SPSS13.0 software was used to analyze the data, P<0.05 was considered as the level of significance.Results:1 The positive staining of Survivin was mostly located in the cytoplasm and/or nucleus,mainly in cytoplasm of cancer cell. The positive rates in RCC were 75.0 %( 28/40),but the positive expression of Survivin wasn't found in the renal tubular epithelia of normal renal tissues (0/5) and the Para carcinoma (0/20). Survivin expressions in RCC were significantly higher than those in normal renal tissues,there was significant difference (P=0.000). The positive expression of Survivin was respectively 77.8%,66.7%,57.1%in clear cell carcinoma,granule cell carcinoma and mixed-cell type; no significant difference was observed among the three groups (P>0.05),and there weren't significant differences between the group with (80.0%) and without lymph nodes metastasis (66.7%) (P>0.05).In G1,G2,G3 grade,the positive rates were respectively 33.3%,79.2% and 85.7%, Survivin expressions had significant difference in the tumor grading(P<0.01).In stage I, II ,III andâ…£the positive rates were respectively 36.4%,78.6%, 80.0%,100%. Survivin expressions had significant difference in the tumor staging(P<0.05), there was significant difference between stage I and II (P<0.05), there was significant difference between stage I,II and III,â…£(P<0.05).2 PTEN showed cytoplasm staining. Normal renal tissues were all positive for PTEN protein. In the corresponding paratumor tissues, 95.0% were positive for PTEN.In the tissues from RCC,it was 65.0% positive for PTEN protein. It was statistically different(P<0.05). The positive expression was 90.9%,85.7%,30.0% and 20.0% in Robson I,II,III andâ…£staging renal carcinoma tissue,there was significant difference between I,II,III and IV staging in statistics(P<0.01),and there was significant difference in Robson I-II(72.7%) and III(28.6%) staging(Fisher's test P<0.05).The positive expression was respectively 63.0%(17/27),66.7%(4/6) and 71.4%(5/7) in renal clear cell carcinoma, granule cell carcinoma and mixed-cell carcinoma, no significant difference was observed in the three groups(P>0.05).PTEN protein expression did not show correlation to sex and age,tumor size and vasculular invasion (P>0.05). PTEN oncoprotein positive staining was found in 81.4% of non lymph node metastasis, PTEN oncoprotein positive staining was found in 30.0% of lymph node metastasis. Robson III-â…£staging with metastasis were significantly lower than those in Robson I-II staging, without metastasis,it has remarkable difference in statistics(Fisher's P<0.05).3 The relationship between the expression of PTEN and Robson staging showed negative rank correlation (P<0.01).With the increase of clinical staging,the expression of PTEN showed degrading in corresponding,whereas the relationship between the expression of Survivin and Robson staging showed positive rank correlation(P<0.01).With the increase of clinical staging, the expression of Survivin showed heightening in corresponding. The relationship between the expression of PTEN and Fuhrman grading also showed negative rank correlation(P<0.05), whereas the relationship between the expression of Survivin and Fuhrman grading showed positive rank correlation(P<0.01)4 Between the expression of PTEN and Survivin showed significantly negative correlation(r=-0.366, P<0.05).The cases of positive expression in Survivin protein showed the high rate of 57.7% in the cases of positive expression of PTEN protein,but in the contrary,it displayed 92.9% of the positive expression of Survivin protein in the cases of low expression of PTEN protein.Conclusions: 1 Survivin showed overexpressions in renal cell carcinoma, but no expressions in normal renal tissues. The expressions of Survivin had no correlation with pathological types, lymph nodes metastasis. But Survivin expression had correlation with tumor staging and tumor grading; the expressions of Survivin in late stages were higher than the early and the intermediate stages. It was revealed that Survivin activation and expression was related to the carcinogenesis and development of renal cell carcinoma,and it could be a marker to evaluate the development and the prognosis of renal cell carcinoma.2 The expressions of PTEN were highly positive in normal renal tissues, but those were low in renal carcinoma. It shows that PTEN may play an important role in renal carcinoma generation and development; the expressions of PTEN were not related to pathological types, but closely related to clinical, pathological grade and lymph nodes metastasis. It could be a marker of the prognosis evaluation.3 Survivin was overexpressed in renal cell cancer but PTEN was reduced.Survivin may play a promoting role and PTEN may play a postponement role in the development of renal cell cancer. Survivin and PTEN may have some relation with aggression and prognosis of renal cell cancer.4 The detection of Survivin and PTEN protein expression may provide useful prognostic information and predict the biological behavior of RCC.Comprehensive analysis of PTEN and Survivin will assist in judgementing biological indicator in RCC.
Keywords/Search Tags:Renal Cell Carcinoma, Survivin, PTEN, expression of protein, immunohistochemistry
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