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The Study Of Clinical Significance Of The Expression Correlation Of PAX2and HIF1αin Renal Clearcell Carcinoma

Posted on:2014-09-20Degree:MasterType:Thesis
Country:ChinaCandidate:Z Y WangFull Text:PDF
GTID:2254330401968875Subject:Surgery
Abstract/Summary:PDF Full Text Request
[Background]:Renal cell carcinoma (RCC) originates from the renal parenchymauriniferous tubule. According to relevant statistics RCC takes3%of the overallincidence of adult malignancies accounted. In China, the incidence of urinary tracttumors is quite high, second only to bladder cancer In early stage there are no obviousclinical symptoms, and when patients come for medical treatment because hematuria,waist mass, they are not in early stage. In recent years, Morbidity and mortality in renalcell carcinoma have increased obviously. Currently, early diagnosis of renal cellcarcinoma mainly is imaging studies, treatment mainly is surgery and prognosis is notwell. Radiotherapy and chemotherapy effects are not well, lack of efficientcomprehensive treatment. The pathological process of the occurrence and developmentof renal cell carcinoma is affected by a variety of gene regulation. Pathogenesis is verycomplex, including mutation and inactivation of tumor suppressor genes or oncogeneactivation. The pathological process of tumor is multi-factor mediated, and a complexprocess of the multi-stage, among which one important factor is the decision due to thecharacteristics of the tumor cells. Excessive proliferation normally makes the tumor in ahypoxic state, while human body cells have a class of transcription factors due tohypoxia, called Hypoxia-inducible factor-1α(HIF1α). These factors stay stable in thehypoxic environment, and Bind to a target gene associated, promote their transcriptionand cause a series of reactions to let human body adapt to the hypoxic environment.These factors relate with tumor vasculature generation, transfer and infiltration, andconsidered to be quite effective. The kidney is a sensitive organ for hypoxia. The kidneytissue in hypoxic environment would produce large amounts of HIF1α, the index ofwhich is significant to kidney diseases. Clear cell of renal cell carcinoma(CCRCC) originate from the renal parenchyma proximal tubule. No matter familial kidney canceror sporadic renal clear cell carcinoma, VH L gene mutation rate is significant high. Therate of the former reaches90%, and the latter reaches50%. CCRCC is oftenaccompanied by von Hippel-Lindau(VHL), which is considered as the result of VHLtumor suppressor gene mutation or loss of expression. Relevant researches reveal thatdue to VHL loss of expression the function decline, the regulatory mechanism ofhypoxia-inducible factor1α activate Pax-2, making its re-expression increase andgenerating abnormal proliferation, and finally leading renal cell carcinoma. This showsthat the pathological process of renal cell carcinoma is quite complicated,co-participated by a variety of factors.[Purpose] This experiment investigate the clinical significance of the expressioncorrelation between Hypoxia-inducible factor1α (HIF1α) and Paired box gene2.Through testing the expression situation of the two in renal cell carcinoma, thisexperiment analyze the relationship between the two and Renal clear cell carcinomatumor size, clinical stage, lymph node metastasis, aiming to provide theoretical basis ofthe early diagnosis of RCC and molecular targeted therapy.[Methods]73experimental specimens were chosen from the archive pathological waxblock specimens of kidney cancer after radical in Anhui Medical University, during2008.05and2012.03. All these experimental specimens have complete clinicalpathological diagnosis and preoperative examination information, and none of thepatients have done relevant preoperative treatments. This experiment also randomlyselected19paracancerous kidney organizations from the73patients. All the specimenswere fixed in10℅formalin solution, and were all pathologically confirmed. Thisexperiment also used immunohistochemistry S-P method to test the expression ofHIF1α and PAX2in Renal cell carcinoma, normal renal tissue next to the cancer and metastatic lymph node tissue through protein levels, and analyze the relationshipbetween HIF1α and PAX2and clinical stage, lymph node metastasis, age, gender, andtumor diameter.[Results] The positive expression rate of PAX2and HIF1α in CCRCC tissue is73.97%(54/73),58.9%(43/73),while the positive expression rate in adjacent normal renaltissue is10.53%(2/19),5.26%(1/19).It indicates that significantly increased both inCCRCC, the positive expression rate than normal kidney tissue next to the carcinoma,the the difference was statistically significant. The experiment results suggest that theexpression of HIF1α and PAX2was relevant with toclinical stage and histologic grade,lymph node status;but nothing to do with age and gender.[Conclusion] The expression of HIF1α and PAX2was relevant with clinical stage andhistologic grade,lymph node status.High expression of HIF1α and PAX2mayimprove the genesis and development of clear cell renal cell cancer,and can be used asan important prognostic index of clear cell renal cell cancer. The coexpression of HIF1αand PAX2may play cooperation role in lymph node metastasis of clear cell renal cellcarcinoma. HIF1α and PAX2could offer the molecular level speculation for assessmentof diagnosis and prognosis in renal cell carcinoma.
Keywords/Search Tags:Clear cell renal cell cancer, HIF1α, PAX2, immunohistochemistry
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