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

Pradhan-Palikhe, Pratikshya; Vesterinen, Tiina; Tarkkanen, Jussi; Leivo, Ilmo; Sorsa, Timo; Salo, Tuula; Mattila, Petri S.

doi:10.1016/j.oraloncology.2010.03.002

« Previous Next »Oral Oncology
Volume 46, Issue 7 , Pages 514-518, July 2010

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

Pratikshya Pradhan-Palikhe
- Department of Oral and Maxillofacial Diseases, Institute of Dentistry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
- These authors contributed equally to this work.
Tiina Vesterinen
- Department of Otorhinolaryngology, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 4 E, P.O. Box 220, 00029 HUS, Finland
- These authors contributed equally to this work.
Jussi Tarkkanen
- Department of Pathology, Helsinki University Central Hospital, Finland
Ilmo Leivo
- Department of Pathology, Helsinki University Central Hospital, Finland
Timo Sorsa
- Department of Oral and Maxillofacial Diseases, Institute of Dentistry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
Tuula Salo
- Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu and Oulu University Hospital, Finland
Petri S. Mattila
- Department of Otorhinolaryngology, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 4 E, P.O. Box 220, 00029 HUS, Finland
- Corresponding author. Tel.: +358 50 4271560.

Received 20 January 2010; received in revised form 3 March 2010; accepted 4 March 2010. published online 05 April 2010.

Summary

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 log¹⁰ 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.

Keywords: Head and neck cancer, Survival, TIMP-1, MMP-8, Genetic polymorphism, Plasma