Recurrence pattern and TP53 mutation in upper urinary tract urothelial carcinoma.
TP53 mutation patterns are associated with prognosis of various cancers. This study was designed to investigate the association between TP53 mutation patterns and recurrence patterns in upper urinary tract urothelial carcinoma (UTUC) patients. A total of 165 consecutive UTUC patients who underwent nephroureterectomies were enrolled for measuring mutation patterns of TP53 gene from exome 2 to 11. Bladder recurrence, contralateral UTUC recurrence, and metastases were compared among groups by using log-rank test and Cox proportional hazard model. Single base substitution as an A:T to T:A transversion was noted in 55 (33.3%) patients (AT group). Forty-two (25.5%) patients had TP53 mutations with only other than A:T to T:A transversion (NAT group), and 68 patients (41.2%) had wide-type TP53 (WT group). AT group was predominately female (64%, 52%, 29%, respectively), had a higher incidence of end-stage renal disease (24%, 14%, 10%, respectively), and had more high-grade tumors (82%, 74%, 62%, respectively) compared to NAT and WT groups. With adjustment of tumor grade/stages, bladder and contralateral UTUC recurrence-free survival duration was shortest in NAT (p < 0.001) and AT group (p < 0.001), respectively. NAT group had a shorter metastasis-free survival duration than the other two groups combined (p = 0.018). As a result, A:T to T:A transversion increased contralateral UTUC recurrence risk, but other mutations in TP53 raised the hazard of bladder recurrence and metastases. Therefore, TP53 mutation pattern may be a useful biomarker to predict recurrence patterns of UTUC patients.
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Chung-Hsin
CH
Chen
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, USA.|Department of Medicine, Stony Brook University, Stony Brook, NY, USA.
Kathleen G
KG
Dickman
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Chao-Yuan
CY
Huang
Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Chia-Tung
CT
Shun
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Huai-Ching
HC
Tai
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Kuo-How
KH
Huang
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Shuo-Meng
SM
Wang
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Yuan-Ju
YJ
Lee
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, USA.|Department of Medicine, Stony Brook University, Stony Brook, NY, USA.
Arthur P
AP
Grollman
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
Yeong-Shiau
YS
Pu
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D016016:Proportional Hazards Models; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
aristolochic acid; cigarette smoking; herbs; renal pelvis; ureter