| Objective:Bladder carcinoma was the most common malignant tumor of urinary system,was also one of the top ten common tumors in human body.90% of bladder carcinomas were bladder urothelial carcinomas(BUC).Bladder urothelial carcinoma grew slowly but relapsed easily.The etiology of Bladder cancer was very complex and is not clear.With the rapid development of molecular research about tumors,it has confirmed that the occurrence of tumor was a gradually evolving process including polygenic participation.And it was closely related.to the activation of oncogene,inactivation of tumor suppressor gene and mutation of repair gene.Therefore,to find new molecular markers was the key to early diagnosis,assessment of the prognosis,prevention of the relapse and setting individualized treatment.Excision repair cross-complementing gene 1(ERCC1)and excision repair cross-complementing gene 2(ERCC2)were two important DNA repair genes.ERCC1 involved in DNA damage identification and DNA excision.Research found that ERCC1 has associated with the development of gastric cancer,non-small cell lung cancer,esophageal cancer,colorectal cancer and bladder cancer.ERCC2 was a necessary enzyme to unlock DNA chain.Recently,the relation between ERCC2 and the process of non-small cell lung cancer has been found.However,the related researches about the relations between ERCC1,ERCC2 and the development process of BUC were rarely.ERBB1 and ERBB2 were two important proto-oncogenes in the family of epidermal growth factor receptor.They played important roles in regulating cell growth,proliferation and differentiation.The over-expression of ERBB1 and ERBB2 would lead to aberrant increase.It has been confirmed that ERBB1 had high expression in non-small cell lung cancer,kidney cancer,colorectal cancer,breast cancer and bladder cancer.ERBB2 has high expression in breast cancer,gastric cancer,ovarian cancer,bladder cancer and other tumors.Wild-type P53 was the most studied tumor suppressor genes.It played an important role in regulating cell cycle,inducing cell apoptosis,inhibiting cell mutation,maintaining normal growth process.Studies have shown that P53 protein is closely related to poor prognosis and the evolution of many tumors.The research about the relation between the co-detection of repair gene ERCC1,ERCC2;oncogene ERBB1,ERBB2;anti-oncogene p53 and bladder cancer has no found.Up to now,no specific biomarker has been reported to be sensitive and specific for bladder cancer detection.The combained detection of varities of genes maybe improve the tumor diagnosis.It has played an important role in the early diagnosis of bladder cancer and evaluating prognosis.The aim of this study was to detect the relationship between expression of ERCC1,ERCC2,ERBB1,ERBB2,P53 and clinical pathological characteristics of bladder cancer,discuss the relationship of these genes in the BUC,further elucidate the roles of these genes and evaluate the clinical significance of the combained detection in bladder cancer,providing scientific theory basis for clinical early diagnosis,treatment and evaluating prognosis.Material and Methods:1 The expression of ERCC1,ERCC2,ERBB1,ERBB2 and P53 were studied with the method of Immunohistochemistry(IHC)to detect in 20 cases normal bladder mucous membrane tissues,26 cases noninvasive low-level papillary urothelial carcinoma,34 cases noninvasive high-level papillary urothelial carcinoma and 48 cases bladder invasive urothelial carcinoma.To analysis the relationship between these genes and the clinical and pathological characteristics;and discuss the relationship of each index in the BUC.2 Statistical analysis: SPSS Statistics16.0 software is applicated.The experimental data are analyzed by Chi-square test,wilcoxon test,spearman correlation analysis,when P< 0.05,the difference was statistically significant.Result:1 Positive immunoreaction of ERCC1,ERCC2 and P53 were located in nucleus and/or cytoplasm.Positive immunohistochemical staining products of ERBB1 and ERBB2 were located in cell membrane and cytoplasm.In 108 cases of bladder urothelial carcinoma tissues,the positive expressions rate of ERCC1,ERCC2,ERBB1,ERBB2 and P53 were 47.1%(51/108),41.7%(45/108),60.2%(65/108),36.1%(39/108)and 66.7%(72/108),respectively.Positive rate of ERCC1,ERCC2,ERBB1,ERBB2 and P53 expressions in 20 cases of normal bladder tissues were 20%(4/20),15%(3/20),10%(2/20),0%(0/20),5%(1/20),respectively.The expressions of ERCC1,ERCC2,ERBB1,ERBB2 and P53 were all higher in bladder cancer tissues than in normal bladder tissues.2 The positive expression rate of ERCC1 was closely related with tumor grade,invasion(P<0.05);but it had no significance with patients’ age,sex,smoking,tumor size,incipient or relapse,single or multiple(P>0.05).3 ERCC2 protein positive expression rate was closely related with tumor grade,invasion(P<0.05);but it had no significance with patients’ age,sex,smoking,tumor size,incipient or relapse,single or multiple(P>0.05).4 ERBB1 protein positive expression rate was closely related with tumor grade,invasion and relapse(P<0.05);but it had no significance with patients’ age,sex,smoking,tumor size,single or multiple(P>0.05).5 ERBB2 protein positive expression rate was closely related with tumor grade and relapse(P<0.05);but it had no significance with patients’ age,invasion,sex,smoking,tumor size,single or multiple(P>0.05).6 P53 protein positive expression rate was closely related with tumor grade and invasion(P<0.05);it had no significance with patients’ age,sex,smoking,tumor size,incipient or relapse,single or multiple(P>0.05).7 ERCC1、ERCC2 and P53 were positively correlated to each other(P<0.05),ERBB1 was positively correlated with ERBB2(P<0.05).No correlation could be found between ERBB1 and P53,between ERBB2 and P53(P>0.05).ERBB1,ERBB2,ERCC1,ERCC2 were no relatios between each other(P>0.05).Conclusion1 In the bladder urothelial carcinoma tissue,the expression of ERCC1,ERCC2,ERBB1,ERBB2 and P53 were associated with the development of BUC,and may become the potential prognostic factor of BUC.2 In the bladder urothelial carcinoma tissue,the expression of ERCC1,ERCC2 and P53 were positively correlated to each other.They may have synergy with each other in the process of the evolution of bladder cancer.3 In the bladder urothelial carcinoma tissue,the expression of ERBB1 and ERBB2 were positively correlated to each other.They may have synergy with each other in the process of the evolution of bladder cancer.4 ERBB1,ERBB2 had a significant correlation with the relapse of bladder urothelial carcinoma,they may become the biomarkers to predict the risk of relapse of BUC.5 Combained detection of ERCC1,ERCC2,ERBB1,ERBB2 and P53 protein in the bladder urothelial carcinoma was benefit to guide the individualized treatment plan for different patient. |
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