MGMT hypermethylation and BCL-2 overexpression associated with superficial bladder cancer and recurrence

Article type: Research Article

Authors: Jahed, Marzieh^a | Ebadi, Nader^a | Mivehchi, Mohamad^a | Majidizadeh, Tayebeh^c | Shahshanipour, Majid^b | Asgari, Mojgan^{d; e} | Ghadakzadeh, Sara^c | Hosseini, Seyed Ali^{c; f; *}

Affiliations: [a] Varamin - Pishva Branch, Islamic Azad University, Varamin, Iran | [b] Department of Urology, Hasheminejad Clinical Research Developing Center, Iran University of Medical Sciences, Tehran, Iran | [c] Department of Genetic Disease, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran | [d] Department of Pathology, Hasheminejad Clinical Research Developing Center, Iran University of Medical Sciences, Tehran, Iran | [e] Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran | [f] Department of Laboratory Medicine, Boston Children Hospital/Harvard Medical School, and Claritas Genomics Inc, MA, USA

Correspondence: [*] Corresponding author: Seyed Ali Hosseini, Department of Laboratory Medicine, Boston Children Hospital/Harvard Medical School, and Claritas Genomics Inc, MA, USA. E-mail:seyedali.hosseini@childrens.harvard.edu

Abstract: 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.

Keywords: Bladder cancer, methylation, tumor suppressor gene, MGMT, BCL-2

DOI: 10.3233/CBM-160604

Journal: Cancer Biomarkers, vol. 16, no. 4, pp. 627-632, 2016