title: [Mismatch repair gene promoter methylation and expression in hydatidiform moles and the malignant transformation].
abstract: OBJECTIVE
  In this study, we assayed promoter hypermethylation and protein expression of the mismatch repair gene (MMR) hMLH1 and hMSH2 in gestational trophoblastic diseases to understand the significance of MMR promoter methylation and expression in the pathogenesis and malignant transformation of hydatidiform mole.
  
  
  METHODS
  DNA was extracted from chorion of early pregnancies, partial hydatidiform moles, complete hydatidiform moles, and invasive moles were over digested by methylation sensitive endonuclease Hpa II. Then the promoters were amplificated by polymerase chain reaction. The protein was detected by immunohistochemistry.
  
  
  RESULTS
  In the normal placenta, neither hMLH1 nor hMSH2 promoter methylation was detected. Expression of hMLH1 and hMSH2 in cytotrophoblasts was strongly positive, and that was negative or weakly positive in syncytiotrophobasts. In all normal chorion, expression of hMLH1 and hMSH2 in cytotrophoblasts was strongly positive. In partial hydatidiform mole and complete hydatidiform mole, the methylation of hMLH1 and hMSH2 promoters was significantly higher than that of early placenta (P < 0.05), and the protein expression in cytotrophoblasts was significantly lower (P < 0.05). In the invasive mole, hMLH1 and hMSH2 promoter methylation were not significantly different as compared with the partial hydatidiform mole and complete hydatidiform mole (P > 0.05). Expression of hMLH1 in the invasive mole (54.5%, 6/11) was not significantly different as compared with the partial hydatidiform mole and complete hydatidiform mole (P > 0.05). But expression of hMSH2 in the invasive mole (36.4%, 4/11) was weaker than that in complete hydatidiform mole (P = 0.044). Promoter methylation and less expression of hMSH2 had correlations in complete hydatidiform mole or invasive mole.
  
  
  CONCLUSIONS
  Strong expressions of hMLH1 and hMSH2 in the cytotrophoblasts of normal placenta may keep the genome stability. Promoter methylation and down-regulation of hMLH1 and hMSH2 are probably involved in the pathogenesis of hydatidiform mole.
authors.affiliation: Department of Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
authors.forename: Chang-kun
authors.initials: CK
authors.lastname: Zhu
authors.forename: Da-feng
authors.initials: DF
authors.lastname: Ye
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Cheng
authors.forename: Huai-zeng
authors.initials: HZ
authors.lastname: Chen
authors.forename: Wei-guo
authors.initials: WG
authors.lastname: Lu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D020137:Base Pair Mismatch / Q000235:genetics*; D002352:Carrier Proteins; D019175:DNA Methylation; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics* / Q000473:pathology; D002820:Hydatidiform Mole, Invasive / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein