title: Prognostic significance of matrix metalloproteinase-9 (MMP-9) in stage II colorectal carcinoma.
abstract: BACKGROUND
  Approximately 30% of all colorectal cancer patients are diagnosed with stage II disease. Adjuvant therapy is not widely recommended. However, it is well-established that a subgroup of patients with stage II is at high risk for recurrence within their life time and should be considered for adjuvant chemotherapy. The present work was designed to assess the value of matrix metalloproteinase-9 (MMP-9) as a predictor of disease outcome in a series of 202 stage II colorectal cancer (CRC) patients with long-term follow-up.
  
  
  METHODS
  The present study comprises a series of 202 patients who underwent bowel resection for stage II CRC at Turku University Hospital. Archival paraffin-embedded CRC tissue samples were used to prepare tissue microarray blocks for immunohistochemical staining with MMP-9 antibody.
  
  
  RESULTS
  Forty-eight percent of all CRC samples were positive for MMP-9. There was no significant correlation between MMP-9 expression and age, depth of invasion, and lymph node status. However, MMP-9 expression was significantly related to histological grade (p = 0.03) and location of the tumor (p = 0.01), therefore, being lower in high-grade tumors and most intense in carcinomas of the descending colon and rectum. Tumors with high MMP-9 expression showed a higher recurrence rate than tumors with low expression (p = 0.02). MMP-9 negative tumors had a more favorable disease-free survival (DFS) than those expressing MMP-9 (p = 0.03). The same was true with disease-specific survival (DSS; p = 0.02) as well, high expression of MMP-9 being associated with shorter survival rates. In multivariate (Cox) survival analysis, MMP-9 expression proved to be an independent predictor of DFS, but not DSS, which was predicted by age and sex only.
  
  
  CONCLUSIONS
  Quantification of MMP-9 expression seems to provide valuable prognostic information in stage II CRC, particularly, in selecting the patients at high risk for recurrent disease who might benefit from adjuvant therapy.
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Hospital, University of Turku, Turku, Finland. abuhme@utu.fi
authors.forename: Abdelbaset
authors.initials: A
authors.lastname: Buhmeida
authors.forename: Riyad
authors.initials: R
authors.lastname: Bendardaf
authors.forename: Marja
authors.initials: M
authors.lastname: Hilska
authors.forename: Yrjö
authors.initials: Y
authors.lastname: Collan
authors.forename: Matti
authors.initials: M
authors.lastname: Laato
authors.forename: Stina
authors.initials: S
authors.lastname: Syrjänen
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
authors.forename: Seppo
authors.initials: S
authors.lastname: Pyrhönen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D020780:Matrix Metalloproteinase 9