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Detection of Slit2 promoter hypermethylation in tissue and serum samples from breast cancer patients

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Abstract

Promoter hypermethylation has been shown to be a common mechanism for inactivation of tumor suppressor genes in breast cancer. The aim of this study was to investigate the prevalence of Slit2 promoter hypermethylation in both the tumor and serum samples of breast cancer patients with ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IBC). The methylation status of Slit2 was investigated in 210 tissue samples (15 breast with no pathological findings, 26 DCIS, and 169 IBC samples) and 123 corresponding serum samples (15 breast with no pathological findings, 26 DCIS, and 82 IBC samples) using methylation-specific polymerase chain reaction. Immunohistochemical staining for Slit2 was also performed using tissue microarray blocks to determine whether Slit2 promoter hypermethylation correlated with loss of Slit2 expression. Slit2 promoter hypermethylation was not detected in breast tissue and serum samples from patients with no pathological findings. DCIS or IBC showed a statistically higher frequency of Slit2 promoter hypermethylation compared to breast with no pathological findings in both the tissue and serum samples; however, there were no statistically significant differences between DCIS and IBC samples. Similar Slit2 promoter hypermethylation patterns were seen in the tissue samples and corresponding serum specimens (p < 0.001). Slit2 promoter hypermethylation was associated with loss of Slit2 expression. These results suggest that Slit2 promoter hypermethylation appears to be responsible for functionally silencing Slit2 expression. Slit2 promoter hypermethylation may be considered as a possible serum marker for early detection of breast cancer.

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Acknowledgements

This study was supported by a grant (CRI10056-1) from Chonnam National University Hospital Research Institute of Clinical Medicine.

We have no conflict of interests to declare.

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Authors and Affiliations

  1. Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea

    Ga-Eon Kim, Kyung Hwa Lee, Yoo Duk Choi, Ji Shin Lee, Jae Hyuk Lee, Jong Hee Nam & Chan Choi

  2. Research Institute of Medical Sciences, Gwangju, Republic of Korea

    Ga-Eon Kim, Kyung Hwa Lee, Yoo Duk Choi, Ji Shin Lee, Jae Hyuk Lee, Jong Hee Nam, Chan Choi, Min Ho Park & Jung Han Yoon

  3. Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea

    Min Ho Park & Jung Han Yoon

  4. Department of Pathology, Chonnam National University Hwasun Hospital, 160, IIsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-809, Republic of Korea

    Ji Shin Lee

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  1. Ga-Eon Kim
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Correspondence to Ji Shin Lee.

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Kim, GE., Lee, K.H., Choi, Y.D. et al. Detection of Slit2 promoter hypermethylation in tissue and serum samples from breast cancer patients. Virchows Arch 459, 383–390 (2011). https://doi.org/10.1007/s00428-011-1143-5

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  • DOI: https://doi.org/10.1007/s00428-011-1143-5

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