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: Pratikshya Pradhan-Palikhe, Tiina Vesterinen, Jussi Tarkkanen, Ilmo Leivo, Timo Sorsa, Tuula Salo, Petri S Mattila
• Journal: Oral oncology (Oral Oncol) Vol. 46 Issue 7 Pg. 514-8 (Jul 2010) ISSN: 1879-0593 [Electronic] England
• PMID: 20371206 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Tissue Inhibitor of Metalloproteinase-2
• Matrix Metalloproteinase 2

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (blood)
• Carcinoma, Squamous Cell (blood, mortality, pathology)
• Female
• Head and Neck Neoplasms (blood, mortality, pathology)
• Humans
• Immunohistochemistry
• Male
• Matrix Metalloproteinase 2 (blood)
• Middle Aged
• Neoplasm Invasiveness
• Predictive Value of Tests
• Prognosis
• Survival Analysis
• Tissue Inhibitor of Metalloproteinase-2 (blood)