title: Alteration of G2 cell cycle regulators occurs during carcinogenesis of the endometrium.
abstract: OBJECTIVE
  In this study, we examined the alteration of the G2 pathway in endometrial hyperplasia (EH) and endometrioid-type endometrial cancer (EC), and analyzed the relationship between the G2 pathway status and the p53 pathway status.
  
  
  METHODS
  A total of 103 cases (proliferative phase of the endometrium: 20, EH: 22, and endometrioid-type EC: 61 (I: 39, II: 5, III: 15, recurrence: 2)) were included in this study. We examined the ATM, chk2, CDC25C, cdc2, and cyclin B1 protein expression by immunohistochemistry. In 55 cases (EH: 15; EC: 40), we analyzed CHK2 mutations by RT-PCR-SSCP.
  
  
  RESULTS
  There were no CHK2 mutations in endometrial disease. Elevated or reduced expression rates of ATM, chk2, CDC25C, cdc2 and cyclin B1 were 4.5% (1/22), 0%, 0%, 0% and 4.5% (1/22) in EH and 3.3% (2/61), 4.9% (3/61), 13.1% (8/61), 9.8% (6/61) and 9.8% (6/61) in EC. Alteration of the G2 pathway was higher in EC (32.8%; 20/61) than in EH (9.1%; 2/22; p = 0.047). The G2 pathway was significantly higher in the altered p53 pathway group (48.4%; 15/31) than in the normal p53 pathway group (16.7%; 5/30) in EC (p = 0.0134). The altered p53 pathway tended to be related with the cdc2/cyclin B1 status (p = 0.0529).
  
  
  CONCLUSIONS
  Alteration of the G2 pathway is thought to occur during carcinogenesis of the endometrium.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka City General Hospital, Osaka, Japan. tsud777@ocgh.hospital.city.osaka.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Hashiguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Kumio
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D016203:CDC2 Protein Kinase / Q000032:analysis; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000737:chemistry; D064447:Checkpoint Kinase 2; D019926:Cyclin B / Q000032:analysis; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000473:pathology*; D004717:Endometrium / Q000737:chemistry* / Q000473:pathology*; D005260:Female; D016195:G2 Phase; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D009154:Mutation; D009367:Neoplasm Staging; D018807:Polymorphism, Single-Stranded Conformational; D011494:Protein Kinases / Q000032:analysis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D025521:Tumor Suppressor Proteins; D020687:cdc25 Phosphatases / Q000032:analysis
chemical_list: C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases