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Open Access Research article

Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

Karina Dahl Steffensen14*, Marianne Waldstrøm2, Rikke Kølby Christensen2, Annette Bartels3, Nils Brünner3 and Anders Jakobsen14

Author Affiliations

1 Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark

2 Department of Pathology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark

3 Department of Veterinary Disease Biology/Section for Pathobiology, Faculty of Life Sciences, University of Copenhagen, Ridebanevej 3, DK-1870 Frederiksberg C, Denmark

4 Institute of Regional Health Services Research, University of Southern Denmark, Winsløwparken 25-3, DK-5000 Odense C, Denmark

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BMC Cancer 2010, 10:185  doi:10.1186/1471-2407-10-185

Published: 7 May 2010

Abstract

Background

Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may therefore play an essential role in the progression of a malignant tumour.

The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment in the individual patient.

Methods

TIMP-1 was assessed by immunohistochemistry (in tissue micro arrays) in a total of 163 ovarian cancer specimens obtained from primary debulking surgery during 1991-1994 as part of a randomized clinical protocol.

Results

Positive TIMP-1 immunoreactivity was found in 12.3% of the tumours. The median survival time for the 143 patients with TIMP-1 negative tumours was 23.7 months [19.0-29.4] 95% CI, while the median survival time for the 20 patients with TIMP-1 positive tumours was 15.9 months [12.3-27.4] 95% CI. Although a difference of 7.8 months in median overall survival in favor of the TIMP-1 tumour negative patients was found, this difference did not reach statistical significance (p = 0.28, Kaplan-Meier, log-rank test). Moreover, TIMP-1 immunoreactivity was not associated with CA125 response (p = 0.53) or response at second look surgery (p = 0.72).

Conclusion

TIMP-1 immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy.