The Correlation Of P53、PCNA And VEGF Protein Expression With Tumor Prognosis In Urothelial Carcinoma Of Bladder

Transitional cell carcinoma of bladder(BTCC) ranking the first of theincidence of urinary system tumors in China, it has increasing trend recentyears.Surgery is the main treatment for bladder cancer (mainly includingtransurethral resection of bladder tumor, partial cystectomy and radicalcystectomy), while giving postoperative adjuvant chemotherapy andimmunotherapy, clinical effect will better, but the high recurrence rate bringchallenges to the clinical. We lack of sensitive and specific prognosticindicator of BTCC, study the reason of bladder carcinogenesis, progress andrecurrence from the molecular and genetic level, has become a hot issue.objective：Tumor markers p53, PCNA or VEGF protein expression in tumors hasbeen discussed, and the use of a single molecule is clearly not enough, In thispaper we study the correlation of three protein expression with bladder tumorgrade, clinical stage and prognosis. We analysis the reasons for the recurrenceof BTCC integrating three tumor markers, expression and other multi-factor.Evaluate if three tumor markers can be used as judgment indicators for thebiological behavior of BTCC and their clinical value. Provide a theoreticalbasis for the clinical diagnosis, treatment and prognosis.Method:Retrospective analysis68cases specimens wax block of surgicaltreatment of bladder transitional cell carcinoma (transitional cell carcinoma ofbladder, BTCC) patient, and32cases postoperative specimens of paraffinblocks by follow-up the patients with recurrence at Affiliated Hospital ofChengde Medical College from January2008to December2011.Allspecimens were pathologically diagnosed as BTCC, select the eight cases of normal bladder epithelial tissue as control, normal mucosa taken from opensurgical specimens of benign prostatic hyperplasia, usingimmunohistochemistry MaxVision method detected the expression of p53,PCNA and VEGF in108cases, the staining results were divided into threelevels, then we analysis their relationship with bladder cancer staging, gradingand recurrence, and the correlation of three kinds protein,using the χ2test orFisher exact test and Spearman rank correlation. The68initial patients werefollowed up for2~40months by telephone, door and other methods, accordingto the UICC-TNM standard there were41cases of superficial(Tis~T1) weretreated with transurethral resection of bladder tumor(TURB-t), infiltrative (T2to T4),27cases of which TURB-t patients five cases, two cases of radicalcystectomy, partial cystectomy20cases; In the32cases of recurrence,3patients died of bladder tumor progress,19cases partial cystectomy,10casesrecieved TURB-t again.In36cases of not recur,2patients died ofcomplications of nonneoplastic,11patients were lost visit. All patients withroutine postoperative within half an hour to give THP infusion chemotherapyimmediately, from one week after the operation began requiring all patients tomaintain perfusion therapy (1times a week,8times,1times a month to2years).The perfusion drug pirarubicin, mitomycin or hydroxycamptothecin andso on. Review cystoscope every3months;19cases without adhering to ourtreatment, remaining49cases had good compliance.Kaplan-Meier methodsurvival analysis was performed on the follow-up cases.Establishment theCOX proportional hazards model of three proteins expression, age, gender,clinical stage, histological grade, number of tumors, whether to adhere to theperfusion medication and other factors affect BTCC recurrence.Results:1Normal bladder tissue and tumor tissueThe three protein positive rate of BTCC was significantly higher thanin normal urothelium (P <0.05).2Primary and recurrence groupsThe positive rate of expression of p53, PCNA and VEGF in recurrence group was significantly higher than the primary group (P <0.05).3The relationship between the expression of p53, PCNA and VEGF andclinicopathological featuresThe positive expression rates of p53、VEGF and PCNA in100cases ofpathological grading, clinical stage were significant different.(P<0.05).Spearman rank correlation analysis showed positive correlation between theover-expression of three protein and tumor pathologic grade、the invasivenessof tumor and tumor recurrence(P<0.05)．4The relationship of p53, PCNA and VEGF in bladder tumor tissuesThe positive correlation was noted between PCNA expression and p53orVEGF expression(P <0.01)．kappa test results show good consistency(P<0.01).p53and VEGF expression rate was weak positive correlation (P <0.05), kappa test results show consistency difference (P <0.05).5Follow-up results of the relationship of three protein and the prognosis ofBTCCThe Kaplan-Meier curves presented that tumors with p53(-) or VEGF(-)phenmype had a favorable outcomes(P<0.05)．The expression of PCNA isclosely correlated with the risk of developing bladder cancer,but not the keyroles(P＞0.05).6Multivariate analysis of BTCC recurrenceOn univariate analysis， the parameters of tumor grade, Clinicalstaging,operative methods,the expression of P53protein and VEGF protein,number of tumors and whether keep intravesical chemotherapy after operationwere significant for tumor recurrence(all P<0.05)．On multivariate analysis ofCOX proportional hazard model,the risk factors for tumor recurrence weretumor stage(RR=4.162，P=0.001)，the expression of P53protein(RR=2.913，P=0.038), the expression of VEGF protein(RR=3.316，P=0.010),long timeintravesical chemotherapy after operation will improve the therapeutic effectof BTCC(RR=0.217，P=0.000)．Conclusion：1P53, PCNA and VEGF protein expression positive rate in BTCC tissue was significantly higher than that of normal urothelial tissue.2The over-expression of VEGF, p53or PCNA is closely related thepathological grading, invasiveness of tumor and prognosis of BTCC, the moreextensive tumor infiltration, the more lower of tumor cell differentiation, theexpression three protein was increased more significant. For the patients ofrecurrence the positive rate was significantly higher than the initial patients.3PCNA and P53expression levels in bladder tumor tissues wassignificantly positively related to good consistency; PCNA and VEGFexpression levels in bladder tumor tissues was significantly positivelycorrelated, in good consistency; the correlation of P53and VEGF expressionlevels was weak, poor consistency. They had interaction effect. P53and VEGFrespectively through different paths induced BTCC recurrence, could be usedas independent indicators of the degree of differentiation of the BTCC andprognosis, while the out of control of PCNA expression involved in theintermediate links of VEGF and p53-induced BTCC recurrence, was theperformance of high value-added state.4Clinical staging, p53and VEGF protein expression are important yetimperfect evaluation of patients with bladder cancer, aside from the key roles,tumor grade, number of tumors and PCNA protein expression are closelycorrelated with the risk of developing bladder cancer. Further intravesicaltherapy also has an associated improved survival.