A1 Refereed original research article in a scientific journal
High levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the serum are associated with poor prognosis in HPV-negative squamous cell oropharyngeal cancer
Authors: Carpén T., Sorsa T., Jouhi L., Tervahartiala T., Haglund C., Syrjänen S., Tarkkanen J., Mohamed H., Mäkitie A., Hagström J., Mattila P.S.
Publisher: SPRINGER
Publication year: 2019
Journal: Cancer Immunology, Immunotherapy
Journal name in source: CANCER IMMUNOLOGY IMMUNOTHERAPY
Journal acronym: CANCER IMMUNOL IMMUN
Volume: 68
Issue: 8
First page : 1263
Last page: 1272
Number of pages: 10
ISSN: 0340-7004
DOI: https://doi.org/10.1007/s00262-019-02362-4
Web address : https://link.springer.com/article/10.1007/s00262-019-02362-4
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/41654684
Background: An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC.
Materials and methods: A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS).
Results: High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels.
Conclusion: Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.
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