Comparison of DNA hypermethylation patterns in different types of uterine cancer: Cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma

Authors

  • Sokbom Kang,

    1. Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
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  • Jae Weon Kim,

    Corresponding author
    1. Department of Obstetrics and Gynecology, Seoul National University, Seoul, Republic of Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
    3. Human Genome Research Institute, Seoul National University, Seoul, Republic of Korea
    • Department of Obstetrics and Gynecology and Cancer Research Institute, Seoul National University, 28 Yungun-Dong, Chongno-Gu, Seoul 110-744, Republic of Korea
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  • Gyeong Hoon Kang,

    1. Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
    2. Department of Pathology, Seoul National University, Seoul, Republic of Korea
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  • Sun Lee,

    1. Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
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  • Noh Hyun Park,

    1. Department of Obstetrics and Gynecology, Seoul National University, Seoul, Republic of Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
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  • Yong Sang Song,

    1. Department of Obstetrics and Gynecology, Seoul National University, Seoul, Republic of Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
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  • Sang Yoon Park,

    1. Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
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  • Soon Beom Kang,

    1. Department of Obstetrics and Gynecology, Seoul National University, Seoul, Republic of Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
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  • Hyo Pyo Lee

    1. Department of Obstetrics and Gynecology, Seoul National University, Seoul, Republic of Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
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Abstract

The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite-modification technique and methylation-specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms. © 2005 Wiley-Liss, Inc.

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