Overexpression of BMI1, a polycomb group repressor protein, in bladder tumors: a preliminary report

A polycomb group repressor protein named BMI1 represses the genes that induce cellular senescence and cell death, and it can contribute to cancer when improperly expressed. We aimed to evaluate expression of BMI1 gene in bladder tumors. Tissue specimens containing bladder tumor were evaluated and compared with intact tissues from tumor margins and normal bladder. These were 40 tumor specimens of patients with transitional cell carcinoma of the bladder, 20 tumor-free tissues taken from the margin of the tumors, and 8 specimens from patients without tumor. Specific primers for BMI1 and B2M [as an internal control] were used for reverse transcript polymerase chain reaction technique. The production and distribution of BMI1 protein was also examined by western blotting and immunohistochemistry techniques. Polymerase chain reaction generated a 683-bp product, corresponding to the expect size of BMI1 amplified region. The identity of the amplified fragment was then confirmed by direct DNA sequencing. The mean of expression of BMI1 detected in tumor tissues was significantly higher than that in intact tissues, and there was also a significant association between the mean of gene expression and the stage of malignancy [P<0.001]. The expression of BMI1 at protein level was further confirmed by western blotting and immunohistochemistry. BMI1 is a potent repressor of retinoblastoma and p53 pathways, and hence, elucidating its role in tumorigenesis is very important. We reported for the first time the expression of BMI1 and its correlation with incidence and progress of bladder tumors

Evaluation of sensitivity and specificity of urine surviving as a new molecular marker in diagnosis of bladder tumors

Bladder cancer is one of the most common forms of cancers in the world. The current gold standards for its diagnosis are cystoscopy and urine cytology. Cystoscopy, a naked eye assessment of the bladder, is invasive, uncomfortable and costly with a great deal of personal variability in its results; while urine cytology has high specificity but low sensitivity, particularly for low-grade lesions. Therefore, there is a need for a molecular tumor marker assay capable of detecting bladder cancer with high sensitivity and specificity. A growing list of tumor markers in urine has been introduced so far, but neither of them has been able to replace the current diagnostic methods. Survivin, an inhibitor of apoptosis [IAP] capable of regulating both cell proliferation and apoptosis, has been recently defined as a universal tumor antigen and as the fourth most significant transcript expressed in human tumors. It has been reported to have 100% sensitivity and 95% specificity for detection of bladder cancer. In the present study, the sensitivity and specificity of survivin as a tumor marker in detecting new and recurrent cases of bladder cancer has been evaluated by nested RT-PCR technique. Our results revealed that survivin could be detected in most patients [11/13, sensitivity=0.84] as well as some healthy volunteers with no obvious sign of bladder cancer [6/13, specificity=0.53]. Also, in this work, for the first time, the presence of two alternatively spliced variants of survivin [survivin-2B and survivin-DEx3] urine is being reported. Interestingly, the presence of survivin-DEx3 was better correlated with malignant lesions of bladder compared to the survivin expression [sensitivity=0.84, specificity=0.92]