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Mismatch repair gene promoter methylation and expression in hydatidiform moles

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Abstract

Methods

In this study, to investigate the significance of mismatch repair genes (MMR) promoter methylation and expression in the pathogenesis and malignant transformation of hydatidiform moles, we assayed promoter methylation and protein expression of the MMR genes hMLH1 and hMSH2 in gestational trophoblastic diseases (GTDs). DNA was extracted from normal placentas, partial hydatidiform moles, complete hydatidiform moles, and invasive moles, over-digested by methylation-sensitive endonuclease Hpa II, and then the promoters were amplificated by polymerase chain reaction. The protein expression was detected by immunohistochemistry.

Results

In the normal placentas, neither hMLH1 nor hMSH2 promoter methylation was detected. Expression of hMLH1 and hMSH2 in cytotrophoblasts was strongly positive. In partial hydatidiform moles and complete hydatidiform moles, hMLH1 and hMSH2 promoter methylation rates were significantly higher than that of normal placentas (P=0.000), and the protein expression in cytotrophoblasts was significantly lower (P=0.000). In the invasive moles, hMLH1 and hMSH2 promoter methylation was not significantly different compared with the partial hydatidiform moles and complete hydatidiform moles (P>0.05). Expression of hMLH1 in the invasive moles (54.5%, 6 out of 11) was not significantly different compared with the partial hydatidiform moles and complete hydatidiform moles (P>0.05). But hMSH2 expression in the invasive moles (36.5%, 4 out of 11) was weaker than that in complete hydatidiform moles (P=0.044). Promoter methylation and less expression of hMSH2 were correlated in complete hydatidiform moles (P=0.001) and invasive moles (P=0.039).

Conclusions

These results indicated that strong expression of hMLH1 and hMSH2 in the cytotrophoblasts of normal placentas may maintain genome stability. Promoter methylation and down-regulation of the expression of hMLH1 and hMSH2 are probably involved in the pathogenesis of hydatidiform moles.

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Authors and Affiliations

  1. Central Laboratory, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China

    Huaizeng Chen

  2. Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China

    Dafeng Ye, Xing Xie, Weiguo Lu, Changkun Zhu & Xiaodong Chen

Authors
  1. Huaizeng Chen
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  2. Dafeng Ye
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  3. Xing Xie
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  4. Weiguo Lu
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  5. Changkun Zhu
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  6. Xiaodong Chen
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Correspondence to Xing Xie.

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Chen, H., Ye, D., Xie, X. et al. Mismatch repair gene promoter methylation and expression in hydatidiform moles. Arch Gynecol Obstet 272, 35–39 (2005). https://doi.org/10.1007/s00404-004-0665-3

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  • DOI: https://doi.org/10.1007/s00404-004-0665-3

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