Prognostic value of plasminogen activator inhibitor-1 in head and neck squamous cell carcinoma.
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.
Speleman
Luciënne
L
Department of Otolaryngology-Head and Neck Surgery, Erasmus MC Daniel den Hoed, Rotterdam, The Netherlands.
Kerrebijn
Jeroen D F
JD
Look
Maxime P
MP
Meeuwis
Cees A
CA
Foekens
John A
JA
Berns
Els M J J
EM
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
D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D016271:Proto-Oncogene Proteins c-myc; D014568:Urokinase-Type Plasminogen Activator; D002402:Cathepsin D