Objective:To investigate the methylation status of the RASSF1A gene promoter in upper tract urothelial carcinoma (UTUC)tissues and its correlation with clinicopathologic characteristics and postoperative recurrence of primary UTUC.Methods:In a retrospective design,a total of 687 patients who underwent surgeries for primary UTUC in the urology department of Peking University First Hospital were enrolled.The methylation status of the RASSF1A gene promoter was analyzed using methylation-sen-sitive polymerase chain reaction on tumor specimens.Results:Aberrant methylation for the RASSF1A gene promoter was detected in 183 (26.6%) DNA samples in total.Aberrant methylation of the RASSF1A gene was strongly associated with tobacco consumption (P =0.044),ipsilateral hydronephrosis (P <0.001 ),tumor location (P <0.001 ),tumor stage (P =0.001 ),tumor grade (P =0.007), lymph node metastasis (P =0.001 )and growth pattern (P =0.013).The methylated RASSF1A gene promoter was an independent risk factor for bladder recurrence (P <0.001,HR =0.471)and contrala-teral recurrence (P =0.030,HR =0.269)of UTUC after surgery.Hypermethylated RASSF1A was pre-dictive for improved bladder recurrence-free survival (BRFS)(P <0.001)and contralateral recurrence-free survival (CRFS)(P =0.021)in the UTUC patients.Compared with the patients with unmethylated RASSF1A,the patients containing tumors with hypermethylated RASSF1A had tendency toward longer re-currence-free survival time [(114.4 ±3.9)months vs.(84.0 ±3.2)months for BRFS,(138.1 ±1.8) months vs.(132.9 ±1.9)months for CRFS]and higher estimated cumulative recurrence-free survive rates (five-year survival rate for example,79.8% ±3.4% vs.57.4% ±2.6% for BRFS,98.9% ± 0.8% vs.93.0% ±1.4% for CRFS).Additionally,tumor multifocality (P =0.002,HR =1.538), and ureteroscopy before surgery (P =0.001,HR =1.725)were independent risk factors for bladder re-currence in postoperative UTUC patients.Conclusion:The methylation status of the RASSF1A gene pro-moter appears to be a promising epigenomic biomarker for assessing the aggressiveness of UTUC and a predictor predicting the urinary tract recurrence after surgery.

Objective: To evaluate the impacts of the prognostic factors of T2N0M0 upper tract urothelial carcinoma (UTUC) for Chinese patients.Methods: A retrospective study was conducted including 235 patients who were diagnosed with T2N0M0 UTUC in our hospital and received radical nephroureterectomy (RNU) or partial ureterectomy during January 2000 and December 2013.The 3 and 5-year can-cer-specific survival rates and bladder recurrence-free survival rates of all the patients were valued using Kaplan-Meier method, and the survival curves with statistical significance between the two were compared using the Log-rank test.Variables with significant differences in the univariate analysis were subjected to the multivariate analysis by Cox regression model.Results: A total of 235 patients were included in this study, including 95 (40.4%) male patients and 140 (59.6%) female patients.The mean age was 66.73±10.49 years.The median follow-up time was 53 (rang: 3-142) months, and during the follow-up, 74 (31.5%) patients died of UTUC after a median of 35 months,and 96 (40.9%) patients developed intravesical recurrence after a median of 19.5 months.The 3 and 5-year cancer-specific survival rates of all the patients were 89.1% and 85.9%, respectively;the bladder recurrence-free survival rates were 85.5% and 80.2%, respectively.The independent prognostic factors of cancer-specific mortality were tumor age elder than 55 years (HR=3.138, 95%CI: 1.348-7.306, P=0.008) and diameter larger than 5 cm (HR=3.320, 95%CI: 1.882-5.857, P<0.001).The independent prognostic factors of bladder recurrence-free survival were ureter tumor (HR=1.757, 95%CI: 1.159-2.664, P=0.008) and lower tumor grade (HR=1.760, 95% CI: 1.151-2.692, P=0.009).Conclusion: T2N0M0 UTUC has a better cancer-specific survival.The intravesical recurrence was equivalent to non-muscle invasive UTUC but earlier.The tumor diameter larger than 5 cm and the patient age elder than 55 years were independently associated with cancer-specific mortality;the primary tumor located in ureter and lower tumor grade were more likely to develop intravesical recurrence.

Objective To assess the gender-related differences of upper tract urothelial carcinoma and analyze the causes of the gender-related differences.Methods We retrospectively studied 942 patients underwent radical nephroureterectomy for upper tract urothelial carcinoma between January 2000 and December 2014 in our hospital.The mean age of the entire cohort was 64.5 years,with 424 males (45.0％)and518 females (55.0％).Compared with male patients,female patients tended to had a history of aristolochic acids exposure (5.2％ vs.11.1％,P =0.001),infrequent smoking (29.7％ vs.5.2％,P ＜0.001) and showed poorer renal function (P =0.023).We reviewed clinicopathologic data from these patients and used univariate analysis to determine the gender-related differences.The Kaplan-Meier method was adopted to investigate the gender differences of cancer specific survival,bladder recurrence-free survival and contralateral upper tract recurrence-free survival of patients.Results When compared with males,females were less likely to have high-stage disease (33.7％ vs.24.9％,P =0.003).The mean follow-up for the entire cohort was 70.2 months (4-193 months).The cancer specific survival rate (x2 =14.116,P ＜0.001)and the contralateral upper urinary tract recurrence rate(x2 =7.362,P =0.007)in females were both higher than those in males.The 5-year cancer specific survival rates were 72.0％ in the males and 83.5％ in females,respectively.In addition,the 5-year contralateral UTUC-free survival rates were 98.6％ in the males and 92.9％ in females.Conclusions Female patients in our cohort were more common and they were more likely to be exposed to aristolochic acids.Females were less likely to have high-stage disease but had significantly worse contralateral upper tract recurrence-free survival.