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The Expression Of Apoptosis Associated Proteins Survivin And Fas In Nephroblastoma And Their Clinical Significance

Posted on:2004-04-10Degree:MasterType:Thesis
Country:ChinaCandidate:Y F SunFull Text:PDF
GTID:2144360092998538Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
Objective: Nephroblastoma(wilms' tumor) is one of the most common malignant solid tumor of childhood which is derived from metanephric blastema. It is the most common renal malignancy of childhood. During the past thirty years, the mortality rate of nephroblastoma has decreased dramatically owing to the proper use of operation, chemotherapy and radiotherapy. However, it does underscore the need to screen survivors for late effects of cancer therapy. Although children seem to tolerate acute toxicities of therapy better than do adults, the growing child may be more vulnerable to the delayed adverse sequelae of cancer therapy, such as effects on growth, fertility, and neuropsychological function. Besides clinical stage and tumor type, there are no recognized biologic markers for predicting prognosis or for guiding treatment, follow-up, and counseling of pediatric patients with nephroblastoma.Survivin is a newly found member of the IAP(inhibitor of apoptosis protein) family, and it is the most intensive inhibitor of apoptosis. Survivin is expressed in multiple tumors and is associated with both unfavorable histology and higher stage of disease. Survivin appears to block default induction of apoptosis during mitosis, and, thus, when overexpressed in cancer cells, survivin may permit aberrant proliferation through mitosis. Although surviving antiapoptosis effects appear to be dependent on microtubule bindingjSurvivin also binds to and inhibits caspase3, a downstream protease in the apoptosis cascade. Angiogenesis is very importment in tumor metastatis. The effect of angiopoietin-1, a key factor in angiogenesis, depending on an abundance of survivin. Unlike survivin , fas is a proapoptotic factor and is a member of the TNF-related family of "death receptors". Fas gene locates on chromosome 10, which encodes a polytide with 319 ammo acide. The ligand of fas is a TNF-associated II type transmembrane protien. The fas system is essential for the balance of cell survive and death. Both immune surveillance cytotoxic T-cells and natural killer cells use this receptor pathway during target cell destruction. The depletion of fas occours in many malignant tumors .So it is important to study the expression of survivin and fas in nephroblastoma, and the relationship between their levels and clinical stage, different outcome ofnephroblastoma. To detect the role of them in the occurance, development of nephroblastoma, and the possible mechanism of tumor cells'invasion and metastasis. In order to evaluate whether they can be used as a reliable predictor for diagnosis and whether a new treatment pattern can be carried out.Method: 30 paraffm-embeded material of nephroblastoma were collected. The control group is composed of 15 specimens of normal kidney tissue acquired from paratumor region of the material. Immunohistochemistry method was used to detect the stain of survivin and fas proteins in normal kidney and nephroblastoma specimens, compare them with clinical stage, pathology type and the ourcome.Result: Positive expression rate of survivin in tumor specimens and significantly higher than that in control (53.3% vs 0.0%, P<0.01), while positive rate of fas in nephroblastoma was lower than that of control(36.6% vs 80.0%, P<0.01). The positive rates of survivn were 83.3%, 45.8% in UH and FH group, and 83.3%, 33.3% in later and early clinical stage respectively. Statistical analysis revealed that expression of survivin in nephroblastoma was significantly correlated with clinical stage and pathological type, but there was not correlationship between fas expression and clinical or pathological stage. In addition, the follow-up data suggested that the survival rate in survivin positive cases was signigicantly lower than that of cases without survivin expression.Conclusion: Both survivin and fas participated in the tumorgenesis of nephroblastoma, and survivin-induced apoptosis inhibition and angiogenesis were significantly associated with the development of nephroblastoma. Expression of survivin may be an important pa...
Keywords/Search Tags:Nephroblastoma, Survivin, Fas, Immunohistochemistry
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