Transforming growth factor beta 1 urokinase-type plasminogen activator andplasminogen activator inhibitor-1 mRNA expression in head and neck squamous carcinoma and normal adjacent mucosa

Background, A balance between urokinase-type plasminogen activator (uPA) an d its main inhibitor type-1 (PAI-1) appears to be important for cancer inva sive behavior, Since uPA/PAI-1 system seems to be regulated by transforming growth factor beta1 (TGF beta1) in different cell types, our aim was to in vestigate the relationship between the expression of the three genes and ly mph node status in head and neck squamous cell carcinomas (HNSCC) at specif ic sites. Materials and Methods. uPA, PAI-1, and TGF beta1 mRNAs were determined by N orthern analysis in tumor, and paired normal mucosa samples were obtained f rom 91 operable HNSCC patients. Results. In oral cavity, excluding tongue, TGF beta1, PAI-1, and uPA mRNAs values were consistently lower in the normal tissues than in tumors. In lar ynx tumors, TGF beta1 expression was increased, but no statistically signif icant differences were found for uPA or PAI-1 mRNAs as compared with normal tissues. Tongue tumors overexpressed only uPA mRNA, and uPA levels showed significant parallel variations with TGF beta1 and PAI-1 mRNAs mainly in pN + tumors. In oral cavity tumors, an inverse correlation between TGF beta1 a nd uPA was observed in pN0 subgroup, elevated uPA mRNA was counterbalanced by high PAI-1 mRNA TGF beta1, and PAI-1 were not coordinately expressed, Co rrelations between the three markers were not found in larynx. Hypopharynx tumors, all staged as pN+, expressed the lowest TGF beta1 mRNA mean values. Conclusions. Combined information about TGF beta1, uPA, and PAI-1 mRNAs may add some clues to the understanding of the pathophysiological role of uPA system in head and neck squamous cell carcinoma. (C) 2001 John Wiley & Sons , Inc.