title: PTP4A3 Independently Predicts Metastasis and Survival in Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Hsin-Chih
authors.initials: HC
authors.lastname: Yeh
authors.affiliation: 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.
authors.forename: Ching-Chia
authors.initials: CC
authors.lastname: Li
authors.affiliation: Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chun-Nung
authors.initials: CN
authors.lastname: Huang
authors.affiliation: Institute of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tzyh-Chyuan
authors.initials: TC
authors.lastname: Hour
authors.affiliation: Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Bi-Wen
authors.initials: BW
authors.lastname: Yeh
authors.affiliation: 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.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Li
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Peir-In
authors.initials: PI
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Lin-Li
authors.initials: LL
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Wen-Jeng
authors.initials: WJ
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000401:mortality / Q000556:secondary*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009367:Neoplasm Staging; D009392:Nephrectomy; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate / Q000639:trends; D013624:Taiwan / Q000453:epidemiology; D014516:Ureteral Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases
keywords: PTP4A3 protein; carcinoma; human; kidney; ureter; urothelium