Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylationReportar como inadecuado

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Journal of Experimental and Clinical Cancer Research

, 34:5

First Online: 22 January 2015Received: 21 October 2014Accepted: 04 January 2015DOI: 10.1186-s13046-015-0120-2

Cite this article as: Zhang, L., Xiong, G., Fang, D. et al. J Exp Clin Cancer Res 2015 34: 5. doi:10.1186-s13046-015-0120-2


BackgroundAberrant methylation of genes is one of the most common epigenetic modifications involved in the development of urothelial carcinoma. However, it is unknown the predictive role of methylation to contralateral new upper tract urothelial carcinoma UTUC after radical nephroureterectomy RNU. We retrospectively investigated the predictive role of DNA methylation and other clinicopathological factors in the contralateral upper tract urothelial carcinoma UTUC recurrence after radical nephroureterectomy RNU in a large single-center cohort of patients.

MethodsIn a retrospective design, methylation of 10 genes was analyzed on tumor specimens belonging to 664 consecutive patients treated by RNU for primary UTUC. Median follow-up was 48 mo range: 3–144 mo. Gene methylation was accessed by methylation-sensitive polymerase chain reaction, and we calculated the methylation index MI, a reflection of the extent of methylation. The log-rank test and Cox regression were used to identify the predictor of contralateral UTUC recurrence.

ResultsThirty 4.5% patients developed a subsequent contralateral UTUC after a median follow-up time of 27.5 range: 2–139 months. Promoter methylation for at least one gene promoter locus was present in 88.9% of UTUC. Fewer methylation and lower MI P = 0.001 were seen in the tumors with contralateral UTUC recurrence than the tumors without contralateral recurrence. High MI P = 0.007 was significantly correlated with poor cancer-specific survival. Multivariate analysis indicated that unmethylated RASSF1A P = 0.039, lack of bladder recurrence prior to contralateral UTUC P = 0.009, history of renal transplantation P < 0.001, and preoperative renal insufficiency P = 0.002 are independent risk factors for contralateral UTUC recurrence after RNU.

ConclusionsOur data suggest a potential role of DNA methylation in predicting contralateral UTUC recurrence after RNU. Such information could help identify patients at high risk of new contralateral UTUC recurrence after RNU who need close surveillance during follow up.

KeywordsMethylation Upper tract urothelial carcinoma Contralateral recurrence Radical nephroureterectomy Predictors AbbreviationsUTUCUpper tract urothelial carcinoma

RNURadical nephroureterectomy

MIMethylation index

CpGCytosine-guanine dinucleotide

CTComputed tomography

MRIMagnetic resonance imaging

eGFREstimated glomerular filtration rate

FFPEFormalin-fixed paraffin-embedded

Lei Zhang and Gengyan Xiong contributed equally to this work.

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Autor: Lei Zhang - Gengyan Xiong - Dong Fang - Xuesong Li - Jin Liu - Weimin Ci - Wei Zhao - Nirmish Singla - Zhisong He - Liqun


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