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Clinical significance of Maspin promoter methylation and loss of its protein expression in invasive ductal breast carcinoma: correlation with VEGF-A and MTA1 expression

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Tumor Biology

Abstract

Maspin is a serine protease inhibitor with tumor-suppressor activity. Maspin can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. Previous studies indicate that the loss of Maspin expression is closely linked to aberrant methylation of the Maspin promoter. We examined the promoter methylation status of Maspin in tumor and corresponding serum of breast cancer patients. In addition, protein expression of this gene was also assessed to determine possible correlation between promoter hypermethylation and gene silencing. Further, we investigated the correlation of Maspin expression with vascular endothelial growth factor (VEGF-A) and MTA1 expression. Maspin methylation was analyzed by methylation-specific PCR in 100 invasive ductal breast carcinoma patients’ tumors and circulating DNA in a prospective study. Promoter hypermethylation was correlated with expression of the encoded protein in tumors by immunohistochemistry. Significant correlation was observed between promoter hypermethylation of Maspin (r = +0.88; p ≤ 0.0001) in tumors and paired sera. Significant association was found between Maspin promoter hypermethylation and loss of its protein expression (p = 0.01, OR = 3.1, 95% CI = 1.3–7.4). The expression of VEGF-A and MTA1 was lower in tumors with high Maspin expression compared to tumors with loss of Maspin expression. Our results indicate that aberrant promoter methylation is associated with loss of Maspin immunoreactivity in breast cancer tissues. Further, loss of Maspin expression is significantly correlated with increased expression of VEGF-A and MTA1.

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Author notes

  1. Ranju Ralhan

    Present address: Joseph and Mildred Sonshine Family Centre for Head and Neck Disease, Mount Sinai Hospital, Joseph and Wolf Lebovic Health Complex, 600 University Avenue, Room 6-416, Toronto, ON, Canada, M5G 1X5

Authors and Affiliations

  1. Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Gayatri Sharma, Sameer Mirza & Ranju Ralhan

  2. Department of Surgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Rajinder Parshad & Anurag Srivastava

  3. Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Siddartha Datta Gupta

  4. Dev Sanskriti Vishwa Vidhyalaya, Hardwar, India

    Gayatri Sharma & Pranav Pandya

  5. Department of Otolaryngology—Head and Neck Surgery, University of Toronto, Toronto, ON, Canada

    Ranju Ralhan

  6. Department of Otolaryngology—Head and Neck Surgery, Mount Sinai Hospital, Joseph and Wolf Lebovic Health Complex, 600 University Avenue, Room 6-416, Toronto, ON, Canada, M5G 1X5

    Ranju Ralhan

  7. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Joseph and Wolf Lebovic Health Complex, 600 University Avenue, Room 6-416, Toronto, ON, Canada, M5G 1X5

    Ranju Ralhan

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  1. Gayatri Sharma
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Correspondence to Ranju Ralhan.

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Sharma, G., Mirza, S., Parshad, R. et al. Clinical significance of Maspin promoter methylation and loss of its protein expression in invasive ductal breast carcinoma: correlation with VEGF-A and MTA1 expression. Tumor Biol. 32, 23–32 (2011). https://doi.org/10.1007/s13277-010-0087-8

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