| P63, a recently identified member of the p53 gene family, encodes multiple products with transactivating, death - inducing and so on. It is well - known that the relationship of p53 mutation with the development of bladder carcinoma and the poor prognosis. But to date few clinicopathological studies on P63 expression in bladder carcinoma has been reported. To better understand the role of p63 in cases of bladder carcinoma, we examined the association of expression of p63 with both clinicopathological features and p53 expression, using immuno-histochemical techniques.Materials and MethodsWe studied 46 transitional cell carcinoma (TCC ) of the bladder patients who had been diagnosed and surgically treated in Department of Urology, the First Affiliated Hospital, China Medical University between 1995 and 1997. Age of the patients ranged from 40 to 72 years ( mean 52 years) , and 26 were men and 20 were women. Tumor grade and stage were performed according to the guideline of International Union Against Cancer ( UICC, 1997 ).Mouse monoclonal antibodies of P63, P53 were bought from Maxin Biotech Inc, fuzhou.Immunohistochemical S - P method and HE staining were performed on all 46 patients. 5 continuous pieces of histological slices of 5um were prepared. Results of immunohistochemical staining were evaluated by a pathologist blinded to all clinical data, and only those cells with nuclear - reactivity were considered positive. To evaluate the protein expression, the results were graded as follows:( + ) over 10% of the neoplastic cells were stained, ( + + + ) over 50% of the neoplastic cells were stained, ( + + ) between 10% and 50% of the neoplastic cells were stained.Chi - square test was used to examine the association between tumor stage, grade and P63, P53 expression. Spearman correlation test was used to test correlation coefficients. The different expression of P63, P53 in survival rates were evaluated by the Kaplan - Meier method and differences were tested by the Log rank test.ResultsThe histological grade 1 occurred in 12 patients, grade 2 in 18 patients, grade 3 in 16 patients. The clinicopathologic tumor stage was T1 in 10 cases, T2 in 15 cases, T3 in 15 cases, and T4 in 6 cases.The positive expression rates of these markers as follows: p63 34.8% (Gl 16.7% ,G2 33. 3% , G3 56. 25% ; Tl 40% , T2 20% , 13 60% , T4 0% ), P53 41. 3% (G1 16.7% ,G2 33.3% ,G3 62.5% ;T1 20% ,T2 26.7% ,T3 46.7% , T4 100% ) Respectively. Statistical analysis revealed close associations of both P63 and P53 with tumor grade (P <0.01) and of P53 with tumor stage(P <0. 05 ). Our study did not show a relationship between P53 expression and P63 expression (rs = 0.48, P = 0. 64).There was a significantly higher P63Using univariate analysis, Kaplan - Meier curves showed that overexpres-sion of P53 has significant differences in survival rates( P <0. 01) , but our stud-y did not demonstrate the association of overexpression of P63 with the poor prognosis( P > 0.05 ).DiscussionRecently, one new member of the P53 family, termed P63 has been identified at 3q27 -29. P63 shares remarkable sequence identity to the DNA - binding , transactivation and oligomerization domains of P53, but contains variableNH2 - and COOH - terminal extensions. When overproduced, P63 can induce Gl cell cycle arrest and/or apoptosis in a P53 - like manner and activate the transcription of P53 -responsive genes, such as P21Wafl, suggesting that they might also be tumor suppressors.P63 encodes multiple products with transactivating, death inducing, and domain - negative activities, which are derived from a single gene with two promoters (TAp63 and A Np63 ) and at last three alternative splicing of the transcripts (a,(Band 7). TAp63 isotypes with the acidic NH2 -terminal transactivating domain can activate transcription of P53 target genes such as P21Wafl, whereas ANp63 isoforms without the trqnsactivating domain can act as domain - negative factors toward transactivation by P53 and P63.P63 is highly expressed in proliferating...
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