Immunohistochemical Determination of ETS-1 Oncoprotein Expression in Urothelial Carcinomas of the Urinary Bladder

Abstract

ETS-1 protooncogene is an important transcription factor that plays a role in the regulation of physiological processes, such as cell proliferation and differentiation. ETS-1 is thought to be related to the growth of carcinoma cells by its regulation of the transcription of matrix metalloproteinases and urokinase-type plasminogen activator. In this study, we aimed to investigate the expression pattern of ETS-1 oncoprotein in urothelial carcinomas of the urinary bladder and determine its relationship with histopathologic parameters, including tumor grade and stage. One hundred six specimens of urothelial carcinoma and a total of 14 normal urothelium were analyzed immunohistochemically with anti-ETS-1 monoclonal antibody. The normal urothelium showed positive ETS-1 immunostaining. ETS-1 expression remained high in low-grade and noninvasive tumors, whereas it frequently decreased in high-grade or invasive carcinomas. Interestingly, ETS-1 was highly expressed in the basal cell layer of the noninvasive urothelial carcinomas. ETS-1 expression showed a strong negative correlation with the tumor grade (P<0.001; r, -0.67) and stage (P<0.001; r, -0.75). The nonmuscle-invasive tumors (pTa+pT1) and noninvasive tumors (pTa) had significantly higher ETS-1 expression than the muscle-invasive tumors (pT2; P<0.001) and invasive tumors (pT1+pT2; P<0.001), respectively. Results of our study show that decreased ETS-1 expression is significantly associated with high grade and advanced stage in urothelial carcinomas of the urinary bladder, and that the downregulation of ETS-1 expression may be a marker of the aggressiveness of such malignancies.

Inhibiting cell migration and cell invasion by silencing the transcription factor ETS-1 in human bladder cancer

“…It should be noted that the results of the correlation of ETS-1 expression with the malignant phenotype of bladder cancer in our study is contrary to the findings from Aysegul S, et al They reported that most of the low-grade and noninvasive bladder cancer largely expressed ETS-1, and that high-grade and invasive bladder cancer showed a frequent decrease or loss of ETS-1expression [ 19 ]. But they only used immunohistochemical staining to investigate the expression of ETS-1 and did not perform the functional experiments in their studies.…”

Review of Ets1 structure, function, and roles in immunity

“…Ets1 is an oncogene whose expression is frequently upregulated in a variety of human tumors of different tissue origins (for example, [115–120]). Using transgenic mouse models, where we are able to inducibly over-express Ets1 in stratified squamous epithelial cells, we have demonstrated that Ets1 induces a number of pro-oncogenic changes when it is expressed in epithelial cells including a block to terminal differentiation accompanied by high secretion of matrix metalloproteases (Mmps), epidermal growth factor ligands, and inflammatory mediators [121, 122].…”

Novel variants inMLLconfer to bladder cancer recurrence identified by whole-exome sequencing

“…ETS1 encodes a member of the ETS family of transcription factor which is involved in stem cell development, cell senescence and death, and tumorigenesis. Sari, Aysegul et al found that non-muscle-invasive tumors had significantly higher ETS1 expression than that of the muscle-invasive tumors [ 40 ], indicating its special role in superficial bladder carcinoma. Additionally, the promoter of telomerase reverse transcriptase ( TERT) gene frequently mutated in bladder carcinoma in which ETS1 bond to the altered promoter and promoted bladder carcinoma migration and progression [ 41 ].…”