期刊
EUROPEAN JOURNAL OF CANCER
卷 46, 期 18, 页码 3233-3242出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2010.07.046
关键词
Colonic neoplasms; Tissue inhibitor of; metalloproteinases 1; Matrix metalloproteinase 9; Immunohistochemistry; Prognostic value of testa; Tumour markers, Biological; Survival rate; Treatment outcome; Disease-free survival; Fluorouracil
类别
资金
- Augustinus Foundation
- Merchant M.Brogaard and wife's Foundation
- Harboe Foundation
- Karen A. Tolstrup Foundation
- Dagmar Marshalls Foundation
- A.P.Moller Foundation for the Advancement of Medical Science
- Hartmann Brothers Foundation
- Director Michael Hermann Nielsen's Foundation
- Manufacturer Einar Willumsen Foundation
- Merchant Sven Hansen and wife Ina Hansen Foundation
- Torben and Alice Frimodt Foundation
- Mastersmith Niels Hansen and wife Foundation
- Director Werner Richter and wife Foundation
- Else and Mogens Wedell-Wedellsborg Foundation
- Danish Medical Association
- Aage Thuesen Bruun and wife Emmy Katy Bruun Memorial Fund
- Desiree and Niels Yde Foundation
- Danish Cancer Society
- Strategic Research Council
- Aase and Ejnar Danielsen Foundation
- Director Jacob Madsen and wife Olga Madsen Foundation
- Director Ib Henriksen Foundation
- Merchant M Kristian Kjaer and wife Foundation
- Foundation of 1870
Aim: To elucidate cellular features accountable for colorectal cancers' (CRC) capability to invade normal tissue and to metastasize, we investigated the level of the collagenase matrix metalloproteinase 9 (MMP-9) and its physiological inhibitor tissue inhibitor of metalloproteinases 1 (TIMP-1) in cancer cells and supporting stroma cells of CRC. Methods: Immunoreactivity of MMP-9 and TIMP-1 by carcinoma cells, lymphocytes and fibroblasts in archival specimens of paraffin-embedded primary tumours were retrospectively associated with outcome in 340 consecutive patients completely resected for CRC stages II-IV and subsequently treated with adjuvant 5-fluorouracil. Results: Expression of MMP-9 by carcinoma cells was demonstrated in 9% of specimens without association to recurrence free survival (RFS) (HR = 1.0; 95% CI: 0.6-1.8; P = 0.9) or overall survival (OS) (HR = 0.9; 95% CI: 0.5-1.6; P = 0.6). TIMP-1 expression by carcinoma cells, which appeared in 64% of the specimens, was inversely related with RFS (HR = 1.3; 95% CI: 0.9-1.8; P = 0.08) and OS (HR = 1.5; 95% CI: 1.1-2.1; P = 0.02). Expression of TIMP-1 by fibroblasts at the invasive border was directly related to RFS (HR = 0.7; 95% CI: 0.6-0.9; P = 0.02) and OS (HR = 0.7; 95% CI: 0.6-1.0; P = 0.05). Expression of MMP-9 by lymphocytes correlated significantly with the degree of peritumoural inflammation (P = 0.02) but not with RFS (HR = 0.9; 95% CI: 0.7-1.1; P = 0.2) or OS (HR = 0.8; 95% CI: 0.7-1.0; P = 0.07). Conclusion: TIMP-1 in cancer cells is associated with poor prognosis independent of its function as inhibitor of MMP-9. MMP-9 and TIMP-1 are important mediators of the host cancer cell interaction in the tumour microenvironment with significant influence on the histopathology and on prognosis of CRC. (C) 2010 Elsevier Ltd. All rights reserved.
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