PTP4A3 Independently Predicts Metastasis and Survival in Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy

Hsin-Chih Yeh; Ching-Chia Li; Chun-Nung Huang; Tzyh-Chyuan Hour; Bi-Wen Yeh; Wei-Ming Li; Peir-In Liang; Lin-Li Chang; Chien-Feng Li; Wen-Jeng Wu

doi:10.1016/j.juro.2015.05.101

PTP4A3 Independently Predicts Metastasis and Survival in Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy

J Urol. 2015 Nov;194(5):1449-55. doi: 10.1016/j.juro.2015.05.101. Epub 2015 Jun 10.

Authors

Affiliations

¹ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
² Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
³ Institute of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan.
⁵ Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁶ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁷ Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan; Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan. Electronic address: angelo.p@yahoo.com.tw.
⁸ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan. Electronic address: wejewu@kmu.edu.tw.

PMID: 26070892
DOI: 10.1016/j.juro.2015.05.101

Abstract

Purpose: Increasing evidence has shown that protein tyrosine phosphatases have dominant roles in setting the levels of tyrosine phosphorylation and promoting oncogenic processes. PTP4A3 has been implicated in cancer metastasis but to our knowledge the role of PTP4A3 in upper tract urothelial carcinoma is unknown. The aim of this study was to investigate the association of PTP4A3 with disease characteristics, distant metastasis and prognosis of upper tract urothelial carcinoma.

Materials and methods: The importance of PTP4A3 was initially examined in paired normal urothelium, noninvasive upper tract urothelial carcinoma, invasive upper tract urothelial carcinoma and nodal metastatic tissue. The PTP4A3 transcript level was assessed in another 20 upper tract urothelial carcinoma samples by real-time reverse transcriptase-polymerase chain reaction. PTP4A3 protein expression was determined by immunohistochemistry using the H-score in 340 upper tract urothelial carcinoma samples. It was further correlated with clinicopathological factors, and disease specific and metastasis-free survival.

Results: The expression of PTP4A3 significantly increased from normal urothelium, noninvasive upper tract urothelial carcinoma and invasive upper tract urothelial carcinoma to nodal metastatic tissue (p <0.001). The PTP4A3 transcript level was also markedly up-regulated in higher stage upper tract urothelial carcinoma (p = 0.002). Over expression of PTP4A3 protein was significantly associated with advanced pT status, nodal metastasis, lymphovascular invasion and perineural invasion (each p <0.001) as well as with inferior disease specific and metastasis-free survival on multivariate analysis (each p <0.0001). In addition, it predicted metastasis in patients with pTa, pT1 and pT2 upper tract urothelial carcinoma.

Conclusions: Results imply that PTP4A3 has a role in the carcinogenesis of upper tract urothelial carcinoma. PTP4A3 over expression independently predicted the metastasis and outcome of upper tract urothelial carcinoma, which was even more important in organ confined disease.

Keywords: PTP4A3 protein; carcinoma; human; kidney; ureter; urothelium.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor / biosynthesis
Biomarkers, Tumor / genetics
Carcinoma, Transitional Cell / diagnosis
Carcinoma, Transitional Cell / mortality
Carcinoma, Transitional Cell / secondary*
Female
Gene Expression Regulation, Neoplastic*
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Metastasis
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / genetics*
Neoplasm Staging
Nephrectomy*
Prognosis
Protein Tyrosine Phosphatases / biosynthesis
Protein Tyrosine Phosphatases / genetics*
RNA, Neoplasm / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Survival Rate / trends
Taiwan / epidemiology
Ureteral Neoplasms / metabolism
Ureteral Neoplasms / mortality
Ureteral Neoplasms / pathology*
Urothelium / metabolism
Urothelium / pathology

Substances

Biomarkers, Tumor
Neoplasm Proteins
RNA, Neoplasm
PTP4A3 protein, human
Protein Tyrosine Phosphatases