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MGMT hypermethylation and BCL-2 overexpression associated with superficial bladder cancer and recurrence
Marzieh Jahed1, Nader Ebadi1, Mohamad Mivehchi1
1Varamin - Pishva Branch, Islamic Azad University, Varamin, Iran.
Background:
Urinary bladder carcinoma is one of the leading causes of death among men, and its high recurrence rates make it one of the most solid tumors to treat. The silencing of the tumor suppressor gene by hypermethylation of the CpG islands and overexpression of proto-oncogene proteins are the main mechanisms in cancers. Here, we investigate methylation status of O6-methylguanine-DNA-methyltransferase (MGMT), a tumor suppressor gene and expression level of BCL-2 a proto-oncogene protein that is frequently observed in bladder carcinoma and its recurrences.
Materials And Methods:
We analyzed the methylation of MGMT in 80 tissue samples of patients suffering from bladder cancer and 80 urine samples of cancer-free individuals by MS-PCR. Additionally, BCL-2 protein expression level was analyzed on these 80 tissue samples by immunohistochemistry.
Results:
45% of patients had MGMT methylation, of which this hypermethylation does not have significant association with an increase in grade, but there was significant association in cases with recurrence tumors and metastasis tumors. Among patients with recurrence tumor, 92.5% patients showed MGMT hypermethylation; 66% of these showed BCL-2 overexpression.
Conclusion:
Our data indicate that MGMT hypermethylation and BCL-2 overexpression may have an intense role in superficial bladder cancer recurrences.
Insights
Hypermethylation of O6-methylguanine-DNA-methyltransferase (MGMT) and BCL-2 overexpression are linked to bladder cancer recurrence. These molecular changes may play a significant role in the progression of superficial bladder tumors.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Urinary bladder carcinoma presents significant mortality and high recurrence rates.
- Gene silencing via CpG island hypermethylation and proto-oncogene overexpression are key cancer mechanisms.
- Investigating O6-methylguanine-DNA-methyltransferase (MGMT) methylation and BCL-2 protein expression in bladder cancer.
Purpose of the Study:
- To investigate the methylation status of the tumor suppressor gene MGMT.
- To analyze the expression level of the proto-oncogene protein BCL-2.
- To determine the association of MGMT methylation and BCL-2 overexpression with bladder cancer recurrence.
Main Methods:
- Analyzed MGMT methylation in 80 bladder cancer tissue samples and 80 urine samples from cancer-free individuals using MS-PCR.
- Assessed BCL-2 protein expression in 80 bladder cancer tissue samples via immunohistochemistry.
Main Results:
- MGMT methylation was observed in 45% of bladder cancer patients.
- MGMT hypermethylation showed a significant association with tumor recurrence and metastasis.
- Among recurrent tumors, 92.5% exhibited MGMT hypermethylation, and 66% of these also showed BCL-2 overexpression.
Conclusions:
- MGMT hypermethylation and BCL-2 overexpression are strongly implicated in the recurrence of superficial bladder cancer.
- These molecular alterations may serve as potential biomarkers for predicting bladder cancer recurrence.
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