الفهرس 
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Abstract
The gram-negative bacterium H. pylori is one of the most common infections in both developing and developed countries that most commonly associated with gastritis, peptic ulcers, and various other gastrointestinal ailments. It infects about 4.4 billion cases around the world and subsequent eradication must be distinct to avoid unnecessary costs and risks. H. pylori infection has been linked more and more often to extragastric malignancies including pancreatic, lung, hepatocellular, and pharyngeal carcinoma. However, association studies reported often controversial and inconclusive results. from another hand, BC is the second most frequent genitourinary malignant disorder and the 10th most frequent tumor. Each year, BC causes about 570000 new cases and nearly 210000 related deaths worldwide. Despite treatment improvement, invasive BC cases mortality didn’t sharply decrease. Better understanding pathogenesis and molecular mechanisms contributing to cancer invasiveness and progression may help improving BC management and treatment. To our best knowledge, no study has been conducted on the impact of co-occurrence of H. pylori infection on BC aggressiveness. Thus, this study aimed to estimate this association using the detection of H. pylori antigen (58 KDa), considering active infection, in patients with BC. We also aimed to evaluate the association between H. pylori antigen and tumor aggressive stages and grades and its association with well-established BC tumor marker, epithelial membrane antigen (EMA). In this study: 1. A total of 95 patients with BC, 75 with benign bladder cystitis and 60 healthy individuals were included. The benign and healthy controls were age- and gender- matched with BC patients. 2. BC patients were classified based on histological grade (22 with Grade I and 73 with Grades II-III) and tumor stage (32 with NMIBC and 63 with MIBC). 3. Using immunoblotting, intense sharp band at 58-kDa was observed in serum samples of BC patients and patients with benign bladder diseases. 4. A total of 62/95 (65.3%) of BC patients were positive for H. pylori antigen compared to 25/75 (33.3%) of patients with benign bladder conditions (P<0.0001). No case of the healthy individuals was positive for H. pylori antigen. 5. Quantitatively, BC patients (0.9±0.15) were associated (P=0.0001) with elevated H. pylori antigen optical density levels compared to patients with benign cystitis (0.25±0.04). 6. Regarding tumor stage, 12/32 (37.5%) of patients with NMIBC were positive for H. pylori antigen while 50/63 (79.4%) of patients with MIBC were positive for H. pylori antigen [P=0.0001; OR (CI)=6.4 (2.5-16.4)]. Also, 8/22 (36.4%) of patients with low-grade BC compared to 54/73 (74.0%) of patients with high-grade BC were positive for H. pylori circulating antigen [P=0.002; OR (CI)=4.9 (1.8-13.7)]. 7. To confirm this association, there was significant correlation between the level of EMA and H. pylori antigen (r=0.577, P=0.0001). Elevated EMA was associated with H. pylori infection in both BC and benign patients. 8. EMA level was higher in patients with MIBC (3.8±0.2 µg/mL) and high grade tumor (3.6±0.2 µg/mL) compared to patients with NMIBC (1.9±0.2 µg/mL) and low grade tumor (2.0±0.3 µg/mL) (P=0.0001). 9. The risk of elevated EMA levels on BC progression in H. pylori infected patients increase compared to non-infected individuals in term of tumor stage (OR=11.5) and grade (OR=12.3). In conclusion, H. pylori antigen was identified at 58-KDa in BC patients using immunoblotting. The antigen was more prevalent in BC patients compared to patients with benign bladder cystitis. Quantitatively, antigen levels were higher in BC patients compared to patients with benign disorders. This association was confirmed using urinary EMA, as established BC biomarker, as BC patients infected with H. pylori were associated with elevated EMA compared to uninfected patients. Elevated EMA was associated with patients with advanced stages and high grades disease.