title: Matrix metalloproteinases expression correlates with survival in patients with esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases capable of degrading the extracellular matrix and play important roles in malignancies. We evaluated the expression of four MMPs in esophageal squamous cell carcinoma (ESCC), and assessed the association between MMP expression and clinicopathologic characteristics and disease-free survival time.
  
  
  METHODS
  We evaluated MMP1, MMP7, MMP9, and MMP13 expression in tissues from 208 patients with ESCC using immunohistochemistry (IHC), and correlated MMP expression to clinicopathologic characteristics and disease-free survival time. To confirm MMP9 expression at different levels, we simultaneously performed RT-PCR, Western blotting, and IHC on tissues from a separate cohort of 23 patients with ESCC.
  
  
  RESULTS
  IHC analysis showed that 63.0%, 41.8%, 49.0%, and 32.2% of 208 ESCC samples were positive for MMP1, MMP7, MMP9, and MMP13, respectively. MMPs were strongly expressed in the cytoplasm of cancer cells, especially in the invasive margin, and weakly expressed in stromal cells. No immunostaining was detected in non-cancerous esophageal mucosa. MMP9 expression was positively associated with poor tumor cell differentiation (p= 0.001), vessel permeation (p= 0.027), and lymph node metastasis (p= 0.027). MMP9 expression was a negative, independent predictor of disease-free survival time (Hazard ratio, 1.470; 95% CI, 1.105 approximately 1.955; p= 0.008). The expression of MMP7 (median survival time: 23 months for MMP7 positive patients, >77 months for MMP7 negative patients; p= 0.001) and MMP13 (median survival time: 18 months for MMP13 positive patients, 39 months for MMP13 negative patients; p= 0.014) correlated negatively with disease-free survival in relatively early stage ESCC patients. Co-expression of MMP7, MMP9, and MMP13 in relatively early stage ESCC samples identified patients with a poor prognosis (13 months median survival time) compared to those lacking MMP7, MMP9, and MMP13 expression (58 months median survival time, p < 0.001).
  
  
  CONCLUSIONS
  MMP9 expression is a negative, independent prognostic factor in ESCC and correlates with tumor cell differentiation, vessel permeation, and lymph node metastasis. MMP7, MMP9, and MMP13 may function in early stage ESCC, and their co-expression predicts poor outcome for relatively early stage ESCC patients.
authors.affiliation: Department of Thoracic Surgery, Pathology, General Surgery, and Genetics, Peking University School of Oncology, Beijing Cancer Hospital, Beijing.
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Gu
authors.forename: Ji-You
authors.initials: JY
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Gu
authors.forename: Xiao-Tian
authors.initials: XT
authors.lastname: Shi
authors.forename: Yang
authors.initials: Y
authors.lastname: Ke
authors.forename: Ke-Neng
authors.initials: KN
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D020782:Matrix Metalloproteinases