Expression Of EZH2 And Its Value In Urothelial Carcinoma Of Bladder And Suprarenal Epithelioma

Bladder tumor is a very common malignancy in urogenital system in China and more than 90% of bladder tumor is urothelial carcinomas of bladder. Despite advances in early detection and treatment of urothelial carcinomas of bladder, many patients with urothelial carcinomas of bladder died from recurrence and metastasis after operation, it lead to bad therapeutic efficacy of urothelial carcinoma of bladder. About 16%-25% palindromic urothelial carcinoma of bladder augment its malignancy level. There will be 10% superficial tumors develop invasive tumors or become metastatic tumors. Some biomarkers may have definite effect on prognosis of urothelial carcinomas of bladder. The patients with bladder cancer may benefit from application of therapy designed according to expression of specific biomarker. Thus, there is a need for novel molecular predictors of tumor behavior at the time of diagnosis that will help guide clinical therapy decision and supervision of tumor development. Renal cell carcinoma (RCC) is one of the malignant tumors which is secondary to carcinoma of urinary bladder in the urinary carcinoma, and renal cell carcinomas of the clear-cell type is the majority tissular type of RCC. It's estimated that the morbility of RCC is increased 2% per annum and about 100,000 patients died from this kind of carcinomas every year in the world. About half members of those patients are in their late stage when they were firstly diagnosed of this cancer, about 40% will be recurrenced after and metabasised before radical renal resection, the survival rate is lower than 3% within 3 years who had not received any treatment. RCC has more malignant and insensitivity to radiotherapy and chemotherapy, and immunotherapy is also has little effect on it. Although radical renal resection is a reliable treatment, but many patients have lost their opportunity for it, this urge us to seek novel molecular predictors of tumor behavior at the time of diagnosis that will help guide clinical therapy decision and supervision of tumor development. The EZH2 is a homolog of the Drosophila Polycomb group (PcG) gene enhancer of zeste, a crucial regulator of homologous gene expression. EZH2 is thought to be involved in the early embryonic development and the control of cellular cycle. Over expression of EZH2 can promote the cell entry to S phase and proliferation as transcriptional repressor. EZH2 was shown to be characteristic by inhibiting the ability of anti-oncogene. Several studies have shown that EZH2 is highly expressed in various tumors and linked to progression of human tumor cells and has been suggested as a novel oncogen. In theory, the suppression of EZH2 expression may inhibit the tumorigeness and metastasis. Our study is to detect the expression of EZH2 in urothelial carcinomas of bladder and suprarenal epithelioma and the relationship with their biology characteristics, and to provid evidence for their diagnosis and therapy.Methods (1)EZH2 mRNA expression and protein expression were assessed in urothelial carcinoma of bladder tissue specmens and normal urothelium by reverse transcription-PCR(RT-PCR) and Immunofluorescene. (2)EZH2 protein expression was assessed by Immunohistochemical method in tissue specimens of nomal nephridium and suprarenal epithelioma. We compare EZH2 expression in two tumor tissue specmens with normal tissue specimens and analyze associativity between EZH2 expression and patho-grading and the clinic stages of two tumors.Results (1)Rates of EZH2 protein expression was 33.3%(4/12)and79.4%(54/68) in the nontumor group and the urothelial carcinoma group respectively by immunofluorescene.EZH2 protein expression was noted in 65%(26/40) of low-grade bladder tumors and 100%(28/28)of high-grade tumor(sP<0.05).Rate of EZH2 protein expression was 68.9%(31/45)in superficial tumors compared with 100% ( 23/23)in invasive tumors (P<0.05).Rates of EZH2 mRNA expression were 25%(3/12) and 84.2%(32/38) respectively in the normal group and the urothelial carcinoma group by RT-PCR. EZH2 mRNA expression was noted in 70.0%(14/20)of low-grade bladder tumors versus 100.0%(18/18) of high-grade tumors(P<0.05).Rate of EZH2 mRNA expression was 72.7%(16/22)in superficial tumors compared with 100.0%(16/16)in invasive tumors (P<0.05). (2)The rate of EZH2 protein expression was 12.5%,74.1%(P<0.05)respectively in the nomal nephridium group and the suprarenal epithelioma group. EZH2 protein expression was increased in localized advanced renal cell carcinoma (â…¢) and metastatic renal cell carcinoma(â…£)compared with localized renal cell carcinoma(â… +â…¡)(P<0.05).There were no marked differences in EZH2 protein expression levels among well-differentiated renal cell carcinoma, moderately differentiated renal cell carcinoma and poorly differentiated renal cell carcinoma .Conclusion (1)Our data show a significant increase in EZH2 expression in urothelial carcinoma of the bladder compared with normal urothelium, and the increased EZH2 expression correlates with patho-grading and the clinic stages of urothelial carcinoma of bladder . These results suggest that EZH2 may play an important role in early diagnosis and preditcting of prognosis for urothelial carcinoma of bladder.(2) Our data show a significant increase in EZH2 expression in suprarenal epithelioma compared with nomal nephridial tissue. These data suggest that increased EZH2 expression correlates with oncogenesis of suprarenal epithelioma. EZH2 may play an important role in early diagnosisand and prognosis for suprarenal epithelioma.