Research Papers:

Recurrence pattern and TP53 mutation in upper urinary tract urothelial carcinoma

Chung-Hsin Chen, Kathleen G. Dickman, Chao-Yuan Huang, Chia-Tung Shun, Huai-Ching Tai, Kuo-How Huang, Shuo-Meng Wang, Yuan-Ju Lee, Arthur P. Grollman and Yeong-Shiau Pu _

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Oncotarget. 2016; 7:45225-45236. https://doi.org/10.18632/oncotarget.9904

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Chung-Hsin Chen1, Kathleen G. Dickman2,3, Chao-Yuan Huang1, Chia-Tung Shun4, Huai-Ching Tai1, Kuo-How Huang1, Shuo-Meng Wang1, Yuan-Ju Lee1, Arthur P. Grollman2,3, Yeong-Shiau Pu1

1Department of Urology, National Taiwan University Hospital, Taipei, Taiwan

2Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, USA

3Department of Medicine, Stony Brook University, Stony Brook, NY, USA

4Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan

Correspondence to:

Yeong-Shiau Pu, email: yspu@ntu.edu.tw

Keywords: aristolochic acid, cigarette smoking, herbs, renal pelvis, ureter

Received: March 26, 2016     Accepted: May 16, 2016     Published: June 07, 2016


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.

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