title: MMP-9 expression varies according to molecular subtypes of breast cancer.
abstract: BACKGROUND
  In 2014, breast cancer remains a major cause of mortality worldwide mostly due to tumor relapse and metastasis. There is currently a great interest in identifying cancer biomarkers and signalling pathways mechanistically related to breast cancer progression. Matrix metalloproteinase-9 (MMP-9) is a member of matrix degrading enzymes involved in cancer development, invasion and metastasis. Our objective was to investigate MMP-9 expression in normal human breast tissue and to compare it to that of breast cancer of various histological grades and molecular subtypes. We also sought to correlate MMP-9 expression with the incidence of metastasis, survival rates and relapse in breast cancer patients.
  
  
  METHODS
  MMP-9 was first studied using in silico analysis on available DNA microarray and RNA sequencing data of human breast cancer tissues and human breast cancer cell lines. We next ascertained MMP-9 expression in both normal breast tissue and in human breast carcinoma tissue microarrays.
  
  
  RESULTS
  Significant increase in MMP-9 expression was found in breast cancer cells where compared to normal breast tissue. A positive correlation could also be established between elevated levels of MMP-9 and breast cancer of high histological grade. Furthermore, our results indicate that not only MMP-9 is differentially expressed between each molecular subset but also, more importantly MMP-9 overexpression revealed itself as a startling feature of triple-negative and HER2-positive breast cancers. Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse.
  
  
  CONCLUSIONS
  Differential expression of MMP-9 reflects the extent of cellular differentiation in breast cancer cells and is closely related to the most aggressive subtypes of breast cancer. Hence, MMP-9 is a promising prognostic biomarker of high-grade breast cancer. In our opinion, MMP-9 expression could help segregate subsets of aggressive breast cancer into clinically meaningful subtypes.
authors.forename: Einas M
authors.initials: EM
authors.lastname: Yousef
authors.forename: Muhammad R
authors.initials: MR
authors.lastname: Tahir
authors.forename: Yves
authors.initials: Y
authors.lastname: St-Pierre
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Canada. louis.gaboury@umontreal.ca.
authors.forename: Louis A
authors.initials: LA
authors.lastname: Gaboury
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D020780:Matrix Metalloproteinase 9; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C579270:MMP9 protein, human