Expression And Interaction Of P53,p21～((WAF1/CIP1) And Cyclin E Genes In Human Bladder Carcinoma And Predictive Value In Tumor Recurrence

Bladder carcinoma is the most common malignant tumor of the genitourinary tract. Superficial bladder tumors frequently recur and progress to invasive disease. Tumor cell proliferation plays an impor-tant role in the development and progression of tliis ,cancer. Activation of oncogejnes and loss of tumor suppressor genes are probably associat-ed with; its,proliferation.The expression of p53 >p21WAF1/CIP1 and cyelin E is different in many tumors, our research is to investigate the corre-lation between, the expressi9n and interaction of. p53 p21WAF1/CIP1 andcyclin E genes in human bladder carcinoma and stheir- predictive valuesin bladder tumor recurreceMaterials and methodsThe study group included 64 patients with transitional cell carci-noma pf ;the bladder, whp were diagnosed at the Department of Urolo-gy, the First AffiUatecl Hospital, China Medical University between 1994 and 1996. FJistplogical grading and staging were performed in accordance with the guidelines of the International Union Against Cancer (UICC, 1R97). The histologieal grade 1 occurred in 12 ca-ses, grade 2 in 35 cases, grade 3 in 17 cases. The clinicopathologic tumor stage was Ta-Tt in 30 cases, T2-T4 in 34 cases, which including male 57, female 7, the average age was 61.3, range from 32-85.Mouse monoclonal antibodies of p53 p21WAF1/CIP1 and Ki-67 Ncyc-lin E were brought from Maxim Biotech Inc, fuzhou.Immunohistochemical S-P method and HE staining were per-formed on all 64 specimens. All slides were reviewed independently by 2 independent pathologist and only those cells with nuclear-reactivi-ty were considered positive. p53 p21WAF1/CIP1 and Ki-67 cyclin E im-munostaining positive cut-off were defined 5% , 5% , 10% , 20% respectively according to previous studies.The relationship among tumor grade, stage, and p53, p21 ,cyclin E or Ki-67 expression were evaluated by chi-squaretest. Correlation coefficients were tested by Spearman correlation test. The prognostic value in tumor recurrence of p53 p21WAFI/CIP1 cyclin E Ki-67 grade stage and tumor diameter were assessed by multivari-ate analysis using the Cox regression analysis model. The different ex-pressions of p53 p21WAFI/CIPI cyclinE Ki-67 in tumor recurrence rates were evaluated by the Kaplan-Meier method and differences were eval-uated by the log rank test.ResultsThe positive expression rates of these markers were as that as fol-lows : P53 43. 8% ; P21WAF1/C1P1 50. 0% ; cyclin E 60.9% ; Ki-67 46. 9% respectively. In our study , significant correlation was found be-tween p53 Ki-67 positive expression and tumor grade and clinical stage. But no significant correlation between cyclin E positive expres-sion and tumor grade and clinical stage was found. Using the spearman correlation test, we found that there was a statistically sig-nificant correlation between p53 and p21WAF1/CIP1 (rs = -0. 630, p = 0.000 ) and p53 and Ki-67 ( rs =0. 371, p = 0.003 ) ; But no corre-lation was-found between p21WAF1/CIP1 and cyclin E (ra=-0.160, p = 0.206 ).Using univariate analysis, Kaplan-Meier curves showed that dif-ferent expressions of p53 cyclin E Ki-67 have significant differences in tumor recurrence rates respectively. In multivariate analysis, using Cox regression analysis model, we found that grade, stage and p53-Ki-67 were statistically significant independent parameter to predict bladder tumor recurrence.DiscussionThe cell cycle progression is usually divided into four phases. They are G₁ SG2 M phases. Cell cycle is regulated by many factors. Cyclins, Cyclin-Dependent Kinases ( CDKs) , and CDK inhibitors have many important regulatory roles during cell cycle. Cyclins D and E belong to the " START" group and are expressed during Gj/S phase. These cyclins complex with CDKs and activate cells into S phase . Expression of cyclin E is maximal at the G,/S transition, its postulated that cyclin E/CDK2 complex control cell cycle entering into S phase.Abnormalities of the p53 tumor suppressor gene have been repor-t...