الفهرس 
Bladder cancerOnly 14 pages are availabe for public view
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Abstract
In Egypt, bladder cancer is the most common form, constituting 30.3% of all cancers. This may be due to endemicity of bilharziasis, which is the major predisposing factor for bladder cancer. The diagnosis and follow up of patients with bladder cancer relies heavily on the use of invasive procedures most commonly cystoscopy with biopsy.
Biochemical measurements of soluble markers in urine provide an avenue that can either complement existing diagnostic methods or be an independent mode of diagnosis. Such measurements are noninvasive and thus can be performed frequently. However, for such diagnostic measurements to be useful they must be highly sensitive and specific. The study of methylation status of the tumor suppressor gene, E-cadherin, may serve as markers for bladder cancer since they are involved in the biology of this cancer. Accordingly, urinary methylated E-cadherin was measured in the present study to examine the usefulness of these markers in detection of bladder cancer in comparison to urine cytology. On the other hand, tumor suppressor gene E-cadherin was previously reported as an independent prognostic factor in this tumor. However, the methylation status of the tumor suppressor gene, E-cadherin, was measured in the present study to examine it’s usefulness as a prognostic factor in an easily obtained urine sample.
This study included 96 male and female subjects. They were classified into three groups:
Group I : including 56 bladder cancer patients.
Group II: including 20 benign bladder lesion patients. Group III: including 20 healthy controls
All patients in our study were subjected to complete detailed history, general and local examinations, routine laboratory investigations, radiodiagnostic investigations as pelvi-abdominal ultrasonography. Patients were examined endoscopically and the tumor was resected by hot loop resection and sent to the pathologist to determine the stage and grade of the tumor.
All subjects were subjected to qualitative detection of bilharzial antibodies in serum, urine cytology, DNA extraction of urine pellets followed by detection of metylated E-cadherin using methylation specific PCR.
Our results revealed the following: positivity rate of urine cytology in different groups of this study showed significant increase in malignant group as compared to benign bladder lesion group and healthy control group (X =21.537, P= 0.000). A significant relationship was observed between the positivity rate of urine cytology and stage and grade (P= 0.034 and 0.019 respectively). The overall urine cytology sensitivity was 48.2 %, specificity was 95 %.
Methylated E-cadherin was analyzed in urine samples from all groups using the MSP technique and there was a statistically significant difference in the positivity rate of methylated E-cadherin between malignant, benign and control groups (X =21.115, P= 0.000). The frequency of the E-cadherin tumor suppressor gene methylation in malignant group was (53.6%). while it was (0%) in non-malignant group and (20%) in benign group. There was a significant association between the positivity rate of urinary methylated E-cadherin and tumor grade (P= 0.029). The urinary methylated E-cadherin showed 53.6 % sensitivity, 90 % specificity.
The methylated E-cadherin was detected in 30 out of 56 malignant patients (53.6%) with a statistical significant association with urine cytology and tumor grade and it was also detected in 4 out of 20 benign patients with old age. This finding is intriguing from the aspect of a possible link between aging, E-cadherin methylation and increased risk for bladder cancer.
In conclusion, the E-cadherin gene is inactivated by genetic and epigenetic mechanisms. Our study demonstrated a frequent methylation of E-cadherin in bladder cancer patients. Detection of gene methylation in routine voided urine using selected markers to be more sensitive than conventional urine cytology.