الفهرس 
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Abstract
Urothelial carcinoma is the most common urinary malignancy with a wide proportion of cancer morbidity and mortality. The most important risk factors for developing bladder cancer are occupational exposure and smoking. The combination of cystoscopy and urine cytology is considered the gold standard in the initial diagnosis of bladder cancer.
This prospective study was subject to joint supervision between Urology and Pathology departments, Menoufia University Hospitals. In this study, we investigated 50 cases of bladder urothelial carcinoma for immunohistochemical expression of P63 and Ki-67 and their correlation with prognostic parameters as grade and stage.
Thirty nine cases were pure urothelial tumors and eleven cases were urothelial carcinoma with squamous differentiation. Seventy percent of cases were superficial at presentation while thirty percent presented with muscle invasive diseases.
The method used for immunostaining was a streptavidin-biotin amplified system. Antibodies used were FLEX monoclonal mouse Anti-Human P63 protein (clone DAK-P63) and Ki-67 antigen (Clone MIB-1).
P63 is the most recently discovered but the most ancient member of the P53 family. It is involved in development, differentiation, and response to cellular stress. P63 exhibits a varied expression pattern in normal tissues. It is expressed at high levels in squamous epithelium and urothelium, as well as the basal cell compartment of glandular epithelium in prostate, breast, and bronchi. High levels of p63 expressed in normal human urothelium are disrupted with progressive loss of urothelial differentiation as tumors advance in both stage and grade.
Forty seven cases (94%) showed nuclear positivity for P63, while three cases (6%) showed negative P63 expression. The percentage of expression ranged between 0.0 and 90.0 % with a mean ± SD of 49.4 ±24.63 and a median of 50.0. This study showed no significant association between P63 expression and tumor stage.
The mean and median values of P63 percentage of expression by bladder urothelial carcinoma cells were higher in low grade tumors (p=0.012).
Besides tumor stage and grade the less definitive prognostic factors for bladder cancer also include tumor size and multifocality. Interestingly the present study showed significant reverse association between P63 expression and number of masses (p=0.037).On the other hand we failed to find significant correlation between P63 expression and other parameters. Ki-67 is a nuclear protein present during different stages of the cell cycles and widely used to assess the activities of cell proliferation in various cancers by immunohistochemistry.
All the studied cases showed nuclear positivity for Ki-67 and the percentage of expression ranged between 5.0% and 70.0 % with a mean ± SD of 35.2 ±20.25 and a median of 35.0. The present study didn‘t show significant correlation between Ki-67 percentage and all the studied parameters but it was observed that Ki67 Expression was elevated with the progression of tumor grade and stage also we observed that the larger tumor had higher Ki- 67 expression. In our study there was no significant correlation between P63 and Ki-67.