Analysis Of Progressive Risk Of T1 Non Muscle Invasive Bladder Cancer

Analysis the clinical features and immunohistochemical informations of T1 non muscle invasive bladder cancer(NMIBC),assess the value of clinicopathological characteristics,biological markers and molecular subtype in predicting the progressive risk of T1 NMIBC.Build a hybrid progression risk model of T1 NMIBC combinating the clinicopathological characteristics and biological markers.Methods: We restrospectively reviewed the clinicopathologic characteristics of 102 patients with T1 NMIBC who received TUR between January 2011 to June 2013 in Tianjin Medical University Cancer Insititute a nd Hospital.Immunohistochemical methods was used to stain all tumor specimens,and TP53,cyclin D1,Ki67,CK20,Her2 expression were scored by the percent of stained cells.The cut off scores of biomarkers were got using receiver operating characteristic curve(ROC).Patients were divided into low and high expression group,and compared the progressive risk between two groups.The prognostic values of these biological markers and clinicopathological characteristics for tumor progressive risk were evaluated by Kaplan-Meier method and constructed cumulative progressive risk curves using SPSS 22.0.Multivariate analysis was performed using Cox hazard models and analyzed the independent prognostic factors.Then we stratified patients according to the number of adverse prognostic factors and build a hybrid progression risk model of T1 NMIBC.On the other hand,according to the expression of biomarkers,divided 93 patients into three subtypes and evaluated the prognostic significance of molecular subtype.P<0.05 was considered statistically significant.Results: 1.Basic clinical features of T1 NMIBC: Of all 102 patients,age from 24 to 88 years old,average age was 55 years old.There were 84 male and 18 female,44(43.1%)cases were without history of smoking and 58(56.9%)cases were with.3cm or more sized tumor were presented in 25(24.5%)cases,77(75.5%)cases less than 3cm.62 cases were single and 40 cases were multiple.76(74.5%)cases were primary and 26(25.5%)were recurrence.There were 15(14.7%)cases concomitant CIS and 87(85.3%)cases without.High grade tumors were found in 38(37.3%)cases,low and median grade(G1,G2)tumors were found in 64(62.3%).Scoring by EORTC, there were 28(27.5%)cases in median risk group and 74(72.5%)in high risk group.2.Follow up results: Progressive time was estimated from surgery,and the follow up deadline was November 2016.There were 14 numbers progressed to MIBC,and the cumulative progressive rate of 1 year,3 year and 5 year were 1%,11.4% and 17.1%.3.Biomarkers expression: Cutoff scores of TP53,cyclin D1,Her2,CK20,and Ki67 is 75%,45%,70%,40% and 25% respectively.10 of 38(26.3%)TP53,4 of 66(6.1%)cyclin D1,7 of 28(25%)Her2,10 of 52(19.2%)CK20,10 of 35(28.6%)Ki67 high expression cases progressed to MIBC.4.Prognostic factors: Univariate analysis found that tumor grade,prior recurrence rate,high expression of TP53,Her2,Ki67 and low expression of cyclin D1 were each significantly associated with tumor progression.Multivariate analysis revealed that prior recurrence rate,high expression of TP53,Ki67 was independent prognostic indicators that predicted tumor progression(P<0.05).5.Hybrid progression risk model: There were 80 cases of low risk group and 22 cases of high risk group,5 cases(6.3%)and 9 cases(23.1%)progressed into MIBC respectively.And the hybrid progression risk model is the independent prognostic indicators of T1 NMIBC.6.Molecular subtype: According to the subtype standard,there were 36 cases of Uro,39 cases of GU,and 18 cases of SCCL.The subtype had relationship with tumor progressive risk(P<0.05).GU and SCCL could combined into one group,and molecular subtype is the independent prognostic indicators of T1 NMIBC.Conclusion: 1.EORTC could not predict the progression of T1 NMIBC accurately.2.Prior recurrence rate,high expression of TP53,Ki67 was independent prognostic indicators that predicted tumor progression.3.Hybrid progression risk model could predict the progression of T1 NMIBC accurately,having a certain clinical application value.4.Molecular subtype of T1 NMIBC is the independent prognostic indicators of progressive risk.It could stratify patients of progressive risk.