DNA hypermethylation of TIMP3 gene in invasive breast ductal carcinoma.

BACKGROUND

Neoplastic cells often display aberrant methylation and silencing of multiple genes, including tumor suppressor genes (TSGs) that regulate critical processes such as cell cycle control, DNA repair and angiogenesis. Tissue inhibitor of metalloproteinase-3 (TIMP3) is an extracellular matrix-bound protein which regulates matrix composition and affects tumor growth, invasion and angiogenesis. It mediates vascular endothelial growth factor (VEGF) by blocking the binding of VEGF to VEGF receptor-2 and inhibits downstream signaling. This study focused on the hypermethylation status of the TIMP3 gene with clinical parameters in invasive breast ductal carcinoma (IDC) samples.

MATERIALS AND METHODS

DNA extraction and methylation specific PCR (MSP) was performed on 173 patients with invasive breast carcinoma. Both specific methylated and unmethylated primers for each gene were used for PCR and the products were visualized on agarose gel. The methylation status of TIMP3 was then compared with corresponding patients' clinicopathologic characteristics.

RESULTS

Methylation frequencies of TIMP3 in the breast cancer samples were 20.81 %. Among the hypermethylated cancers, 50% were tumor grade II-III, 44.44% were positive in lymph node involvement (LN), 36.11% were positive in lymphovascular permeation (LVP); 44.44%, 22.22% and 47.22% for the overexpressions in estrogen receptor (ER), progesterone receptor(PR) and c-erbB2, respectively.

CONCLUSION

The result demonstrated that hypermethylation of TIMP3 in IDC might be associated with high tumor grading and lymph nodes metastasis, and overexpression of ER, PR and c-erbB2, respectively.