title: Plasma level of tissue inhibitor of matrix metalloproteinase-1 but not that of matrix metalloproteinase-8 predicts survival in head and neck squamous cell cancer.
abstract: Expression of matrix metalloproteinase-8 (MMP-8) in tongue cancer cells has been associated with an improved prognosis. MMP-8 is inhibited by tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and elevated levels of TIMP-1 in blood have been associated with poor prognosis in many cancers. We wished to evaluate the usefulness of peripheral blood MMP-8 and TIMP-1 levels as well as the genotypes of MMP8 and TIMP1 in predicting prognosis in head and neck squamous cell carcinoma (HNSCC). Plasma concentrations of MMP-8 and TIMP-1 were analyzed in 136 HNSCC patients. MMP8 and TIMP1 genotypes were determined by analysis of single nucleotide polymorphisms (SNP) in peripheral blood DNA. The mean follow-up time was 3.3years. We found that plasma MMP-8 level did not predict survival but that TIMP-1 level was associated with survival. The adjusted hazard ratio of death scored as a continuous variable on the log(10) scale was 23.2 (95% CI 1.88-286, P=0.01) and that of MMP-8 1.24 (95% CI 0.54-2.84, P=0.61). Immunohistochemical staining showed that TIMP-1 was expressed in vascular endothelium of tumor. TIMP-1 levels were associated with TIMP1 genotype in women but not in men. MMP8 genotype did not correlate with survival or MMP-8 level. Plasma TIMP-1 levels predict survival in HNSCC. TIMP-1 expression is genetically controlled in women. As TIMP-1 inhibits the activity of MMP-8 and it also functions as a growth factor, it may directly influence HNSCC progression.
authors.affiliation: Department of Oral and Maxillofacial Diseases, Institute of Dentistry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Pratikshya
authors.initials: P
authors.lastname: Pradhan-Palikhe
authors.forename: Tiina
authors.initials: T
authors.lastname: Vesterinen
authors.forename: Jussi
authors.initials: J
authors.lastname: Tarkkanen
authors.forename: Ilmo
authors.initials: I
authors.lastname: Leivo
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
authors.forename: Petri S
authors.initials: PS
authors.lastname: Mattila
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000401:mortality / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2