title: Inactivation of O⁶-methyguanine-DNA methyltransferase by promoter hypermethylation: association of epithelial ovarian carcinogenesis in specific histological types.
abstract: OBJECTIVE
  The aim of this study was to evaluate O⁶-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation, MGMT expression and microsatellite instability (MSI), as well as to elucidate their correlation with clinical and pathological parameters in epithelial ovarian cancer.
  
  
  METHODS
  Ovarian cancer tissue specimens (n = 86) were obtained after a staging operation. The MGMT gene was investigated by methylation-specific polymerase chain reaction (MSP) and MGMT expression status was analyzed using immunohistochemistry. MSI status was examined by the fluorescence-based PCR using five National Cancer Institute markers.
  
  
  RESULTS
  Negative MGMT expression was detected in 12 of 86 (14.0%) epithelial ovarian cancers. In 34 cases where MSP results were available, MGMT promoter hypermethylation was detected in five cases (14.7%) with mucinous or clear cell carcinomas, but not in any of other histological types (P = 0.031). Five out of six cases with negative MGMT expression showed MGMT promoter hypermethylation, whereas all of the 28 cases that retained expression of MGMT were unmethylated at the MGMT CpG island (P < 0.001). In 41 cases of MSI results available, seven (17.1%) cases showed MSI-H-phenotyped. Both MGMT promoter hypermethylation and negative MGMT expression were noted only in cases of mucinous or clear cell carcinoma in which MSI status were mostly MSS-phenotyped; however, no significant correlation was found between MSI status and clinicopathological parameters.
  
  
  CONCLUSIONS
  Negative MGMT expression was significantly correlated with MGMT promoter hypermethylation in MSS-phenotyped tumors of mucinous or clear cell carcinoma. The results suggest that MGMT promoter hypermethylation might be associated with epithelial ovarian carcinogenesis in specific histological types.
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors: Hyun-Jin
authors: HJ
authors: Roh
authors: Dong-Soo
authors: DS
authors: Suh
authors: Kyung-Un
authors: KU
authors: Choi
authors: Hang-Jo
authors: HJ
authors: Yoo
authors: Won-Deok
authors: WD
authors: Joo
authors: Man-Soo
authors: MS
authors: Yoon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; D019853:O(6)-Methylguanine-DNA Methyltransferase