Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract
AbstractUsing preclinical models, we have recently found that ELK1, a transcriptional factor that activates downstream targets, including c-fos proto-oncogene, induces bladder cancer outgrowth. Here, we immunohistochemically determined the expression status of phospho-ELK1, an activated form of ELK1, in upper urinary tract urothelial carcinoma (UUTUC). Overall, phospho-ELK1 was positive in 47 (47.5%; 37 weak (1+) and 10 moderate (2+)) of 99 UUTUCs, which was significantly (P = 0.002) higher than in benign urothelium (21 (25.3%) of 83; 17 1+ and 4 2+) and was also associated with androgen receptor expression (P = 0.001). Thirteen (35.1%) of 37 non-muscle-invasive versus 34 (54.8%) of 62 muscle-invasive UUTUCs (P = 0.065) were immunoreactive for phospho-ELK1. Lymphovascular invasion was significantly (P = 0.014) more often seen in phospho-ELK1(2+) tumors (80.0%) than in phospho-ELK1(0/1+) tumors (36.0%). There were no statistically significant associations between phospho-ELK1 expression and tumor grade, presence of concurrent carcinoma in situ or hydronephrosis, or pN status. Kaplan-Meier and log-rank tests revealed that patients with phospho-ELK1(2+) tumor had marginally and significantly higher risks of disease progression (P = 0.055) and cancer-specific mortality (P = 0.008), respectively, compared to those with phospho-ELK1(0/1+) tumor. The current results thus support our previous observations in bladder cancer and further suggest that phospho-ELK1 overexpression serves as a predictor of poor prognosis in patients with UUTUC. View Full-Text
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Inoue, S.; Ide, H.; Fujita, K.; Mizushima, T.; Jiang, G.; Kawahara, T.; Yamaguchi, S.; Fushimi, H.; Nonomura, N.; Miyamoto, H. Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract. Int. J. Mol. Sci. 2018, 19, 777.
Inoue S, Ide H, Fujita K, Mizushima T, Jiang G, Kawahara T, Yamaguchi S, Fushimi H, Nonomura N, Miyamoto H. Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract. International Journal of Molecular Sciences. 2018; 19(3):777.Chicago/Turabian Style
Inoue, Satoshi; Ide, Hiroki; Fujita, Kazutoshi; Mizushima, Taichi; Jiang, Guiyang; Kawahara, Takashi; Yamaguchi, Seiji; Fushimi, Hiroaki; Nonomura, Norio; Miyamoto, Hiroshi. 2018. "Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract." Int. J. Mol. Sci. 19, no. 3: 777.
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