Serum MMPs and TIMPs: may be predictors of breast carcinogenesis?

Abstract

Background: The involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in breast cancer has been documented on palpable lesions. This study aims to assess serum MMP1, MMP-2, TIMP-1, and TIMP-2 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specifically in non-palpable mammographic breast lesions.

Methods: On women with benign (n=65), precursor [ADH (n=18) and LN (n=15)], preinvasive [DCIS (n=32)] and invasive [IDC (n=28)] lesions the serum concentrations of MMP-1, MMP-2, TIMP-1, TIMP-2, TPS, and TPA were determined with immunoenzymatic assays. All women had non-palpable mammographic breast lesions of less than 10mm in diameter, as estimated on the mammographic views. Statistical analysis followed.

Results: TIMP-2 serum concentrations were positively associated with the severity of the lesion. On the contrary, MMP-2 levels were marginally negatively associated with severity; as evident, the MMP-2/TIMP-2 ratio significantly decreased along with severity. Regarding TIMP-1, TPS, TPA, and TIMP-1/TIMP-2, no significant associations were demonstrated. MMP-2 and the MMP-2/TIMP-2 ratio were significantly higher in the LN subgroup versus the ADH subgroup.

Conclusion: TIMP-2 and MMP-2/TIMP-2 ratio may exhibit meaningful changes along with progression of lesions. Extracellular cell matrix remodeling in ductal and lobular lesions may follow distinct patterns.