title: Expression of MMP and TIMP mRNA in peripheral blood leukocytes of patients with invasive ductal carcinoma of the breast.
abstract: OBJECTIVE
  An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) appears critical for tumor progression and metastasis. This study aimed to determine whether gene expression of MMP1, MMP2, MMP9, TIMP1 and TIMP3 and the MMP/TIMP expression ratio in peripheral blood leukocytes (PBLs) and the MMP1 and TIMP1 contents or MMP1/TIMP1 ratio in plasma were associated with clinicopathological characteristics in invasive ductal carcinoma (IDC) of the breast.
  
  
  METHODS
  Blood samples were collected from women newly diagnosed with IDC who had not received prior treatment (n = 102). Gene expression in PBLs was analyzed by quantitative real-time polymerase chain reaction. Concentrations of MMP1 and TIMP1 in plasma were measured using ELISA.
  
  
  RESULTS
  In univariate analysis the expression levels of MMP2 and TIMP1 mRNA were significantly higher in premenopausal compared to postmenopausal patients (p&lt;0.001 and p = 0.014, respectively). MMP2 mRNA expression negatively correlated with age (p&lt;0.001, r = -0.43). We found that the MMP2/TIMP3 expression ratio was significantly higher in women after menopause (p = 0.007). The MMP2/TIMP1 expression ratio was higher in human epidermal growth factor receptor 2 (HER2)-positive patients (p = 0.022). Low-grade tumors had significantly lower MMP1/TIMP1 and MMP2/TIMP1 expression ratios (p = 0.047 and p = 0.048, respectively). TIMP1 plasma concentration was significantly higher in small tumors compared with T2-T3 tumors (p = 0.013).
  
  
  CONCLUSIONS
  These findings reveal an important association between tumor characteristics and expression ratios of MMP1/TIMP1 and MMP2/TIMP1 in PBLs and TIMP1 concentration in plasma. Menopausal status may influence the mRNA expression levels of MMP2 and TIMP1 as well as the MMP2/TIMP3 expression ratio in IDC of the breast.
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz - Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Wieczorek
authors.affiliation: Copernicus Memorial Hospital, Department of Surgical Oncology, Lodz - Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Galicki
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University, Lodz - Poland.
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Tomasik
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz - Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Krol
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz - Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Jablonska
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University, Lodz - Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fendler
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz - Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gromadzinska
authors.affiliation: Copernicus Memorial Hospital, Department of Surgical Oncology, Lodz - Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Morawiec
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz - Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wasowicz
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz - Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Reszka
mesh_terms: D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases