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The Relationship Between Tumor Metastasis Suppressor Gene KAI1 And Differentiation, Infiltration And Metastasis Of Bladder Transitional Cell Carcinoma

Posted on:2005-01-03Degree:MasterType:Thesis
Country:ChinaCandidate:R L LiuFull Text:PDF
GTID:2144360125957790Subject:Urology
Abstract/Summary:PDF Full Text Request
Objectives Bladder cancer is the most common malignant tumor in the urological system ,whose morbidity is going up recently ,morbidity and mortality are both at the first place in the urological system of our country. More than 90% is bladder transitional cell carcinoma (BTCC), which has the characteristics of multifocus, heterogeneity, recurrence and infiltration, threatening people's health severely. Approximately, 80% of all the BTCC are superficial cancer which recur easily after operation , the recurrence rate is 50%~70% at the first year after local excision. About 10%~30% superficial cancer can develop into invasive cancer besides the primarily invasive cancer. And the main reason that lower the living standard and cause death of the patients with cancer is the recurrence and metastasis of tumor. Therefore, how to lessen the invasion and metastasis of tumor is most important besides preventing the recurrence of tumor. Recently, molecular biology study showed that the metastasis was a multi-stepped complex experience which involved the interaction among the tumor cells, host cells and extracellular matrix. The whole process was modulated by its metastatic gene and metastasis suppressor gene, and metastasis suppressor gene was the gene that can prevent the metastasis of tumor and not affect the growth of the primary tumors. KAI1, CD44, MAPK kinase 4 and NM23 were the genes which related to the metastatic suppression of tumors. Of all the genes, KAI1 was a newly discovered one. Because it was firstly discovered in the prostatic carcinoma, KAI1 was defined as the prostatic carcinoma metastasis suppressor gene. After that, its metastatic suppression to lung cancer, pancreas cancer, breast cancer,colon cancer, melanoma and esophagus cancer were discovered. But the relationship between KAII gene and BTCC is not clearly understood. In the present study, we detected the expression of KAII protein and KAII mRNA in BTCC and normal bladder tissue, meanwhile, detecting the proliferation activity through Ki67, to try to explore the relationship between KAII gene and BTCC metastasis, hoping to provide a new target for clinically evaluating metastatic potential and estimating prognosis of BTCC, simultaneously, providing a new way to the therapy of tumor metastasis.Materials and Methods Tissues were obtained from 54 patients who underwent open surgery ,TURBT and biopsy in the first affiliated hospital of Zhengzhou University from Sep,2002 to Aug, 2003. 32 normal specimens were obtained at the same time from the aforesaid patients. All the BTCC tissues were pathologically confirmed and no patient had received radiotherapy, chemotherapy and immunotherapy before operation. There were 36 males and 18 females, the age ranged from 32 to 76 years old (mean: 61.5 years old). All the specimens were cut into two, one was put into liquid nitrogen, the other was fixed with 10% formalin and embedded routinely with paraffin, every section was 4Mm. 32 specimens were superficial in nature (Tjs~Ti), 22 specimens were invasive (T2~T4) according to UICC-TNM staging system. 21 specimens belong to Grade I; 16, Grade II; 17, Grade III according to WHO. Multiclonal rabbit anti-KAIl and monoclonal mouse anti-Ki67 nuclear antigen were used to detect the expression of KAII protein and Ki67 antigen in BTCC and normal bladder tissues by two-stepped immunohistochemistry staining. KAII protein was recorded with percentage (the rate of positive cells to all the cells): >51% was positive (++); 5%~50% was weak positive (+); <5% was negative (-). Ki67 antigen was indicated with Ki67 labelling index (Ki67LI), Ki67LI = positive cells/ all the cells x 100%. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the KAIlmRNA in the same tissues, p-actin was the internal contrast. The level of the KAII mRNA was indicated relatively with optic density of electrophoresis fragments of cDNA, namely, KAII cDNA/p-actin cDNA. SPSS 10.0 software was used to analyze the data, a = 0.05 was considered the level of significance.Results 1. KAIlmRN...
Keywords/Search Tags:Bladder transitional cell carcinoma, Metastasis suppressor gene, Metastasis, KAI1 gene, Ki67, RT-PCR
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