title: Clinical implications of proteolytic activity imbalance in breast cancer diagnosis.
abstract: BACKGROUND
  Matrix metalloproteinase-9 and its tissue inhibitor TIMP-1 have been documented as putative tumor markers because of their involvement in cancer invasion and metastasis.
  
  
  OBJECTIVE
  The aim of our study was to elucidate the diagnostic efficacy of proteolytic activity markers among traditional tumor markers (CEA and CA15.3) and clinicopathological variables.
  
  
  METHODS
  Serum samples were withdrawn from 160 individuals (80 patients with primary breast cancer, 40 patients with benign breast lesions and 40 individuals serve as healthy controls). MMP-9 and TIMP-1 were measured by ELISA and gelatin zymography.
  
  
  RESULTS
  The best cutoff points for MMP-9 and TIMP-1 were depicted by receiver operating characteristic (ROC) curve. The positivity rates and the median levels for MMP-9 and TIMP-1 showed significant difference among the three investigated groups (P< 0.0001). MMP-9 and MMP-9/TIMP-1 were inversely related to clinical stage and lymph node involvement (P< 0.0001). TIMP-1 was significantly correlated with hormonal receptor status (ER, and PgR). MMP zymography results were comparable to those from ELISA. The sensitivity and the specificity of MMP-9, TIMP-1 and MMP-9/TIMP-1 were superior to traditional tumor markers (CEA and CA15.3) especially for early stages (T1) and low grade breast cancer patients.
  
  
  CONCLUSIONS
  These findings indicate that investigated biomarkers are constructive for early diagnosis of breast cancer and MMP-9/TIMP-1 ratio might be a new significant marker in predicting breast cancer development.
authors.affiliation: Department of Biochemistry, Genetic Engineering and Biotechnology Research Division, National Research Center, Dokki, Giza, Egypt.
authors.forename: Menha
authors.initials: M
authors.lastname: Swellam
authors.affiliation: Department of Biochemistry, Faculty of Science, Beni-suef University, Beni-Suef, Egypt.
authors.forename: Hanan A
authors.initials: HA
authors.lastname: Soliman
authors.affiliation: Department of Biochemistry, Genetic Engineering and Biotechnology Research Division, National Research Center, Dokki, Giza, Egypt.
authors.forename: Mohamed D E
authors.initials: MD
authors.lastname: Abdelmaksoud
authors.affiliation: Department of Biochemistry, Genetic Engineering and Biotechnology Research Division, National Research Center, Dokki, Giza, Egypt.
authors.forename: Amira M
authors.initials: AM
authors.lastname: Nageeb
authors.affiliation: Radiation Oncology and Nuclear Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Lobna R Ezz
authors.initials: LR
authors.lastname: El Arab
authors.affiliation: Deptartment of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Hussein
authors.initials: H
authors.lastname: Boshnak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D011956:Receptors, Cell Surface; D019715:Tissue Inhibitor of Metalloproteinase-1; C065686:carcinoembryonic antigen binding protein, human; D010447:Peptide Hydrolases; D020780:Matrix Metalloproteinase 9
keywords: Breast cancer; MMP-9; TIMP-1; early diagnosis; zymography