Résumé
Objective:To validate gender-related differences in patients with upper tract urothelial carcinoma (UTUC).Methods:We used a method of combination of SEER database analysis and validation in our center. We selected 2 125 men (57.8%) and 1 552 (42.2%) women who underwent radical nephroureterectomy (RNU) for UTUC between 1995 and 2015 within the surveillance, Epidemiology, and End Results registries (SEER). In male cases, the median age was 71(22-99)years old, median follow-up time was 53.0 (0-227) months, 902 (89.5%) cases were Caucasian, 1 384 cases (65.1%) were located in the renal pelvis, and 810(38.1%) cases were T 3-T 4. For female cases, the median age was 73.6(25-99)years old, median follow-up time was 53.1(0-226) months, 1 417(91.3%) cases were Caucasian, 1 043 cases (67.2%) were located in the renal pelvis, and 508 (32.7%) cases were T 3-T 4. The analysis of SEER database showed that female patients were older compared to male patients ( P=0.002), the proportion of T 3-T 4 was even lower ( P=0.028). There were no statistically significant differences in race, tumor location, and follow-up time between males and females (all P>0.05). We also enrolled 131 men (55.3%) and 106 women (44.7%) who underwent RNU for non-muscle invasive (T a/T is/T 1) UTUC between January 2000 and January 2015. These patients had no history of bladder cancer, UTUC and kidney transplantation. Preoperative cystoscopy was performed to confirm the absence of bladder tumor. The male group was (65.8±12.4)years old, with history of aristolochic acid medications in 7(5.3%) cases, 98 smoking cases (74.8%), and estimated glomerular filtration rate (eGFR) of (64.2±29.4)ml/(min·1.73 m 2). In the female group, mean age was (66.7±11.9)years, 14 (13.2%) cases had history of aristolochic acid medications, 16(15.1%) had history of smoking, eGFR (56.3±27.9) ml/(min·1.73m 2). Compared with female patients, male patients tended to had less aristolochic acids exposure (5.3% vs.13.2%, P<0.001), frequent smoking (74.8% vs. 15.1%, P<0.001) and better renal function ( P=0.036). The Kaplan-Meier test was used for time-to-event analysis. Univariate and multivariate logistic regression models were adopted to examine the effect of gender on the development of T 3-T 4 tumor. Univariate and multivariate Cox regression analyses were used to assess the roles of factors on overall survival (OS) in both SEER and cases in our center, and competing-risks regression model was used to assess the roles of factors on cancer-specific survival (CSS) in both SEER and cases in our center. Results:Multivariate logistic analysis showed that gendere represented an independent risk factor of T 3-T 4 UTUC development( OR=0.86, P=0.02). Kaplan-Meier analysis showed that better OS and CSS for females only existed in the non-muscle invasive stages(5-year OS rates were 80.4% vs.87.3%, χ 2=31.0, P<0.001; 5-year CSS rates were 82.6% vs.89.2%, χ 2=31.2, P<0.001). In multivariate competing-risks regression models, no statistically significant differences in survival were observed between males and females ( HR=0.83, P=0.115). For the patients in our center, there were also no statistically significant differences existed in the non-muscle invasive stage between two genders on OS and CSS ( HR=0.93, P=0.071; HR=0.87, P=0.064). Conclusions:Females were less likely to have advanced pathological T stage. The differences on OS and CSS between males and females only existed in non-muscle invasive stage. However, after accounting for gender related factors, gender no longer had effects on UTUC prognosis.
Résumé
Objective To investigate the expression of proline rich tyrosine kinase 2 (Pyk2) in non-muscle invasive bladder cancer,and analyze its correlation to clinicopathologic features and prognosis of non-muscle invasive bladder cancer.Methods 114 surgical specimens and 50 normal bladder mucosa specimens were collected from 114 non-muscle invasive bladder cancer patients who underwent TURBT at our hospital,from June 2013 to March 2018.Of the 114 patients,63 were male and 51 were female,aged 42-87 years,average age of (63.6 ± 13.8) years,73 cases of tumor ＜3 cm,41 cases of tumor ≥3 cm,83 cases were single and 31 cases were multiple tumor,53 cases were high grade and 61 cases were low grade,59 cases were Ta and 55 cases were T1 stage.Pyk2 protein expression was detected by immunohistochemistry and western blot.The correlation of the expression of Pyk2 with clinicopathologic features,including gender,age,tumor size,the number of tumors,histological grade and clinical stage were analyzed.Survival analysis was calculated by using the Kaplan-Meier method,and the difference in survival curve was analyzed by using the log-rank test.Association of Pyk2 expression with prognosis of non-muscle invasive bladder cancer analyzed by using the Cox proportional hazards regression model.Results Compared with normal bladder tissues,expression of Pyk2 protein was increased in bladder cancer tissue significantly(0.571 ±0.230 vs.0.253 ± 0.152,P ＜0.01).The expression of Pyk2 protein was closely related to clinical stage(P =0.027) and grade(P =0.010),rather than gender (P =0.275),age (P =0.419),tumor size (P =0.317),and tumor number(P =0.208).The recurrence rate in the Pyk2 positive group and negative group were 46.1％ (35/76)and 28.9％ (11/38)respectively.The progression rate in the Pyk2 positive group and negative group were 35.5％ (27/76) and 10.5 ％ (4/38) respectively.Survival analysis suggested expression of Pyk2 in non-muscle invasive bladder cancer had a significant relation to recurrence-free survival rate(P ＜0.001) and progression-free survival rate(P =0.003).In the multivariable Cox analysis,we found that Pyk2 protein was an independent predictor of recurrence-free survival rate(HR 0.245,95％ CI 0.078-0.768,P =0.016) and progression-free survival rate (HR 0.095,95％ CI 0.012-0.764,P =0.027).Conclusions The expression of Pyk2 in non-muscle invasive bladder cancer was significantly increased.The expression of Pyk2 has a significant relation to recurrence and progression of non-muscle invasive bladder cancer.High Pyk2 expression is an independent prognostic factor in non-muscle invasive bladder cancer.