Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract
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 upp...
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doaj-1693337820c448fb8cdf4a22fd6afff72020-11-25T00:50:09ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-03-0119377710.3390/ijms19030777ijms19030777Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary TractSatoshi Inoue0Hiroki Ide1Kazutoshi Fujita2Taichi Mizushima3Guiyang Jiang4Takashi Kawahara5Seiji Yamaguchi6Hiroaki Fushimi7Norio Nonomura8Hiroshi Miyamoto9Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Pathology and James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Urology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanDepartment of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Urology, Osaka General Medical Center, Osaka 558-8558, JapanDepartment of Pathology, Osaka General Medical Center, Osaka 558-8558, JapanDepartment of Urology, Osaka University Graduate School of Medicine, Suita 565-0871, JapanDepartment of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USAUsing 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.http://www.mdpi.com/1422-0067/19/3/777ELK1immunohistochemistryupper urinary tract urothelial carcinomaprognosisandrogen receptor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Satoshi Inoue Hiroki Ide Kazutoshi Fujita Taichi Mizushima Guiyang Jiang Takashi Kawahara Seiji Yamaguchi Hiroaki Fushimi Norio Nonomura Hiroshi Miyamoto |
spellingShingle |
Satoshi Inoue Hiroki Ide Kazutoshi Fujita Taichi Mizushima Guiyang Jiang Takashi Kawahara Seiji Yamaguchi Hiroaki Fushimi Norio Nonomura Hiroshi Miyamoto Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract International Journal of Molecular Sciences ELK1 immunohistochemistry upper urinary tract urothelial carcinoma prognosis androgen receptor |
author_facet |
Satoshi Inoue Hiroki Ide Kazutoshi Fujita Taichi Mizushima Guiyang Jiang Takashi Kawahara Seiji Yamaguchi Hiroaki Fushimi Norio Nonomura Hiroshi Miyamoto |
author_sort |
Satoshi Inoue |
title |
Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract |
title_short |
Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract |
title_full |
Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract |
title_fullStr |
Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract |
title_full_unstemmed |
Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract |
title_sort |
expression of phospho-elk1 and its prognostic significance in urothelial carcinoma of the upper urinary tract |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-03-01 |
description |
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. |
topic |
ELK1 immunohistochemistry upper urinary tract urothelial carcinoma prognosis androgen receptor |
url |
http://www.mdpi.com/1422-0067/19/3/777 |
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