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Int. J. Mol. Sci. 2018, 19(3), 777; https://doi.org/10.3390/ijms19030777

Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract

1
Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
2
James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA
3
Department of Pathology and James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
4
Department of Urology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan
5
Department of Urology, Osaka General Medical Center, Osaka 558-8558, Japan
6
Department of Pathology, Osaka General Medical Center, Osaka 558-8558, Japan
7
Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA
*
Author to whom correspondence should be addressed.
Received: 20 February 2018 / Revised: 28 February 2018 / Accepted: 6 March 2018 / Published: 8 March 2018
(This article belongs to the Special Issue Sex Hormone Receptor Signals in Human Malignancies)
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Abstract

Using 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
Keywords: ELK1; immunohistochemistry; upper urinary tract urothelial carcinoma; prognosis; androgen receptor ELK1; immunohistochemistry; upper urinary tract urothelial carcinoma; prognosis; androgen receptor
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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.

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