title: MGMT hypermethylation and BCL-2 overexpression associated with superficial bladder cancer and recurrence.
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.
  
  
  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.
  
  
  CONCLUSIONS
  Our data indicate that MGMT hypermethylation and BCL-2 overexpression may have an intense role in superficial bladder cancer recurrences.
authors.affiliation: Varamin - Pishva Branch, Islamic Azad University, Varamin, Iran.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Jahed
authors.affiliation: Varamin - Pishva Branch, Islamic Azad University, Varamin, Iran.
authors.forename: Nader
authors.initials: N
authors.lastname: Ebadi
authors.affiliation: Varamin - Pishva Branch, Islamic Azad University, Varamin, Iran.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mivehchi
authors.affiliation: Department of Genetic Disease, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Tayebeh
authors.initials: T
authors.lastname: Majidizadeh
authors.affiliation: Department of Urology, Hasheminejad Clinical Research Developing Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Shahshanipour
authors.affiliation: Department of Pathology, Hasheminejad Clinical Research Developing Center, Iran University of Medical Sciences, Tehran, Iran.|Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Asgari
authors.affiliation: Department of Genetic Disease, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Ghadakzadeh
authors.affiliation: Department of Genetic Disease, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.|Department of Laboratory Medicine, Boston Children Hospital/Harvard Medical School, and Claritas Genomics Inc, MA, USA.
authors.forename: Seyed Ali
authors.initials: SA
authors.lastname: Hosseini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016017:Odds Ratio; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: BCL-2; Bladder cancer; MGMT; methylation; tumor suppressor gene