title: Prognostic value of plasminogen activator inhibitor-1 in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Tumor cell biological factors, such as urokinase plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor-1 (PAI-1), cathepsin D, and c-myc play a role in tumor invasion, metastasis, and proliferation. In this study, the prognostic importance of these factors in patients with primary head and neck squamous cell carcinoma (HNSCC) was evaluated and correlated with clinicopathologic variables.
  
  
  METHODS
  In 46 paired primary tumors and normal tissues, levels of uPA, PAI-1, cathepsin D, and c-myc amplification were determined. The clinical follow-up was over 10 years. Relationships between cell biological factors and patient and tumor characteristics were studied by the Mann-Whitney test. The Cox proportional hazard model was used for univariate and multivariate analysis.
  
  
  RESULTS
  In this study, only a high level of PAI-1 was associated with a significantly shorter disease-free survival (p < .01). PAI-1 levels were higher in tumors with perineural invasion (p < .01). Both PAI-1 and uPA levels were higher in patients who smoked (p < .01 and p = .02). In univariate analysis, smoking (p= .04), excessive alcohol intake (p = .02), perineural invasion (p = .001), and vaso-invasion (p = .009) were associated with a shorter disease-free survival. The only factor related to overall survival was perineural invasion (p = .045). The combination of a high PAI-1 level and perineural invasion appeared to be a significant predictor of a shorter disease-free interval (p = .01).
  
  
  CONCLUSIONS
  PAI-1 may present a novel prognostic factor for patients with HNSCC. Perineural invasion and PAI-1 level combined seemed to be prognostic for disease-free survival.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Erasmus MC Daniel den Hoed, Rotterdam, The Netherlands.
authors.forename: Luciënne
authors.initials: L
authors.lastname: Speleman
authors.forename: Jeroen D F
authors.initials: JD
authors.lastname: Kerrebijn
authors.forename: Maxime P
authors.initials: MP
authors.lastname: Look
authors.forename: Cees A
authors.initials: CA
authors.lastname: Meeuwis
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.forename: Els M J J
authors.initials: EM
authors.lastname: Berns
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality; D002402:Cathepsin D / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D015996:Survival Rate; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D016271:Proto-Oncogene Proteins c-myc; D014568:Urokinase-Type Plasminogen Activator; D002402:Cathepsin D