الفهرس 
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Abstract
Bladder cancer is the fourth most common cancer occurring in United States, second most prevalent cancer in men and tenth most prevalent cancer in women, with age adjusted incidence rate of 24.5 per 100.000 population and mortality rate of 4.2 per 100.000 population per year (Pashos et al., 2002). Because of its high recurrence rate, the actual prevalence of active bladder cancer is estimated to be about 10 times the number of new cases. (Stein et al., 2001).
In Egypt, urinary bladder carcinoma is one of the most common malignancies. Its prevalence is 10.1% according to the last National Cancer institute registry 2003- 2004 (Mokhtar et al., 2007),
The wingless-type (Wnt) pathway plays a central role in embryonic development. Aberrant activation of the Wnt pathway contributes to the progression of several major human cancers. Therefore, inhibition of Wnt effects has major therapeutic potential (Tang, 2009).
β-Catenin is a protein that in humans is encoded by the CTNNB1 gene which can function as an oncogene (Wissmann et al., 2003).Activation of the Wnt/β- catenin signaling pathway by aberrant accumulation of stabilized β-catenin can be involved in the development of many neoplasmes (Björklund et al., 2008).
This study aims at investigating β-catenin protein expression in bladder urothelial carcinoma and its possible relation to the clinico-pathological data.
This study was carried out on 80 patients, 20 patients with chronic non specific cystitis as a control group and 60 patients of Urothelial bladder cancer.
We correlated the expression of this marker in urothelial cancer with different clinicopathological features that may affect the prognosis of these tumors.
Histopathological examination of the UBC group revealed that 26 of UBC cases (43.3%) were of low grade tumor while 34 (56.7%) cases were of high grade. Regarding muscle invasion, 30 cases (50%) were non muscle invasive, muscle invasion observed in 30 cases (50%) of UBC. Lymph nodes show tumor metastasis in 17 cases (28.3%) while negative in 43 cases (71.7%). In our study we had 30 (50%) cases of early stages, stage I and II, and 30 cases (50%) of advanced stages, stage III and IV. Perineural invasion were observed in 20 cases (33.3%), while 40 (66.6%) cases shows no perineural invasion. 48 cases (80%) of UBC specimens show no vascular Invasion and only 12cases (20%) were associated with vascular invasion. Tumor cell necrosis was seen in 12 (15%) UBC cases. Nine out of 60 (15%) UBC cases showed bilharzial infection.
Urothelium adjacent to urothelial carcinoma were available in 9 cases, this urothelium showed epithelial dysplasia ranged from mild to severe one. None of them showed squamous metaplasia.
Six (30%) patients of the control group members showed positive β-catenin expression. while forteen (70%) patients were on the negative side. All the β-catenin positive cases of the control group showed cytoplasmic localization. Regarding the intensity of β-catenin expression in positive cases, 4 of them showed low β- catenin score while 2 cases had a high score.
Fourty (66.7%) cases of the UBC group were positive for β-catenin while 20 (33.3%) cases were on the negative side. Thirty of the β-catenin positive cases showed nucleocytoplasmic localization and 21 cases showed high intensity of its expression.
Comparison between control group and malignant one regarding β-catenin expression, revealed a statistically significant difference (P=0.008) where cases of UBC showed higher rate of β-catenin expression. Furthermore, the maliganant group is significantly associated with Neucleo-cytoplasmic pattern of β-catenin expression.
Forty of UBC cases were positive for β-catenin expression and only 20 cases were negative. Thirty of positive cases showed nucleocytoplasmic localization while the remaining 10 showed cytoplasmic localization. There was a highly a significant difference between β-catenin expression and .tumor grade (P=0.03) ,lymph node metastasis (P=0.005), tumor necrosis (P=0.001) vascular invasion(P=0.004) and perineural invasion (P=0.001).
No statistical significant relation was found between β-catenin expression either bilharziasis (P=0.08), muscle invasion (p=0.54), or stage (p=0.7).
Correlation between localization of β-catenin positivity in UBC cases and the demographic parameters revealed a statistically significant (P=0.004) difference between pattern of β-catenin expression and patients age. Also, Nucleocytoplasmic localization of β-catenin expression showed a highly significant association with higher tumor grade (P=0.006), advanced stage(P=0.02), bilharziasis (P=0.02) and tumor necrosis (P=0.032)
But there was no statistical significant relation between β-catenin localization and either vascular invasion(P=0.65), or mitosis (P=0.5)
There was a statistical significant difference between both pattern of expression of β-catenin and lymph node metastasis (P = 0.038). But there was no statistical significant relation between β-catenin localization and either bilharziasis (P = 0.146), or tumor necrosis (P = 0.459).
Correlation between the intensity of β-catenin expression and patient age revealed 19 Cases with low score and a median of 60 years while 21 cases with high score and a median of 62 years. The difference between both groups was not statistically significant (P 0.42).
Regarding the sex, no statistically significant difference were found between both categories where 19 (52.8%) of males were associated with low β-catenin score and 17 (47.2 %) cases were associated with high score. On the other hand 5(41.7 %) of females were associated with low score and 7 (58.3 %) cases associated with high score.
There was a highly significant difference between high β-catenin score and tumor grade (P = 0.001), lymph node metastasis (P = 0.004), stage (P = 0.001), vascular invasion (P = 0.004), perineural invasion (P = 0.001), mitosis (P = 0.001) and MVD (P= 0.001). High β-catenin score was significantly associated with muscle invasion (p = 0.036).
Evaluation of β-catenin expression in dysplastic urothelium adjacent to tumor revealed 7 out of 9 positive cases. β-Catenin expression showed nucleocytoplasmic pattern of expression and it was mild in 5 cases and high in 2 cases.