Tumor Biology

, Volume 32, Issue 1, pp 23–32

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

  • Gayatri Sharma
  • Sameer Mirza
  • Rajinder Parshad
  • Anurag Srivastava
  • Siddartha Datta Gupta
  • Pranav Pandya
  • Ranju Ralhan
Research Article

DOI: 10.1007/s13277-010-0087-8

Cite this article as:
Sharma, G., Mirza, S., Parshad, R. et al. Tumor Biol. (2011) 32: 23. doi:10.1007/s13277-010-0087-8

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.

Keywords

Breast cancerDNA methylationMaspinMTA1Gene silencing

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Gayatri Sharma
    • 1
    • 4
  • Sameer Mirza
    • 1
  • Rajinder Parshad
    • 2
  • Anurag Srivastava
    • 2
  • Siddartha Datta Gupta
    • 3
  • Pranav Pandya
    • 4
  • Ranju Ralhan
    • 1
    • 5
    • 6
    • 7
    • 8
  1. 1.Department of BiochemistryAll India Institute of Medical SciencesAnsari NagarIndia
  2. 2.Department of SurgeryAll India Institute of Medical SciencesAnsari NagarIndia
  3. 3.Department of PathologyAll India Institute of Medical SciencesAnsari NagarIndia
  4. 4.Dev Sanskriti Vishwa VidhyalayaHardwarIndia
  5. 5.Department of Otolaryngology—Head and Neck SurgeryUniversity of TorontoTorontoCanada
  6. 6.Joseph and Mildred Sonshine Family Centre for Head and Neck DiseaseMount Sinai Hospital, Joseph and Wolf Lebovic Health ComplexTorontoCanada
  7. 7.Department of Otolaryngology—Head and Neck SurgeryMount Sinai Hospital, Joseph and Wolf Lebovic Health ComplexTorontoCanada
  8. 8.Department of Pathology and Laboratory MedicineMount Sinai Hospital, Joseph and Wolf Lebovic Health ComplexTorontoCanada