Enhanced mRNA expression of tissue inhibitor of metalloproteinase‐1 (TIMP‐1) in breast carcinomas is correlated with adverse prognosis

Nakopoulou, Lydia; Giannopoulou, Ioanna; Stefanaki, Kalliopi; Panayotopoulou, Effie; Tsirmpa, Ioanna; Alexandrou, Paraskevi; Mavrommatis, J.; Katsarou, Sophia; Davaris, Panagiotis

doi:10.1002/path.1129

Cited by 78 publications

(72 citation statements)

References 30 publications

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“…In the evaluation of TIMP-1 as a prognostic marker in breast cancer, various methodologies have been used. Early studies measured TIMP-1 protein levels in tumor tissue by enzyme linked immunosorbent assay (ELISA) [10], or evaluated mRNA content [9] whereas later studies focused on TIMP-1 protein levels in blood [18,19] or evaluation by IHC [8,11,16]. Most studies fi nd high TIMP-1 protein levels to be associated with poor prognosis whereas only one study reports high TIMP-1 protein levels to be associated with good prognosis [11].…”

Section: Discussionmentioning

confidence: 99%

Association of tissue inhibitor of metalloproteinases-1 and Ki67 in estrogen receptor positive breast cancer

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Association of tissue inhibitor of metalloproteinases-1 and Ki67 in estrogen receptor positive breast cancer

et al. 2012

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“…Nevertheless, it has been suggested that the coexpression of various MMPs and/or tissular inhibitors of metalloproteinases (TIMPs) might provide additional prognostic information in breast cancer. Accordingly, it has been reported that several other MMPs and TIMPs may be overexpressed and/or related to clinical outcome in breast cancer, such as MMP-11 MT1-MMP (MMP-14) (Jones et al, 1999;Mimori et al, 2001) MMP-13 (Nielsen et al, 2001), TIMP-1 (Ree et al, 1997;McCarthy et al, 1999;Nakopoulou et al, 2002a;Schrohl et al, 2003Schrohl et al, , 2004 or TIMP-2 (Visscher et al, 1994;Ree et al, 1997;Remacle et al, 2000). In addition, there are at least two elements adding more complexity to the role of MMPs and TIMPs in cancer.…”

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confidence: 99%

Overexpression of matrix metalloproteinases and their inhibitors in mononuclear inflammatory cells in breast cancer correlates with metastasis-relapse

et al. 2007

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An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinase (MMP)-1, -2, -7, -9, -11, -13 and -14, tissular inhibitors of metalloproteinase (TIMP)-1, -2 and -3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast were performed. To identify specific groups of tumours with distinct expression profiles the data were analysed by unsupervised hierarchical cluster analysis by each cellular type. We did not find well-defined cluster of cases for tumour cells or fibroblastic cells. However, for mononuclear inflammatory cells the dendogram shows a first-order division of the tumours into two distinct MMP/TIMP molecular profiles, designated group 1 (n ¼ 89) and group 2 (n ¼ 42). Matrix metalloproteinase-7, -9, -11, -13 and -14, and TIMP-1 and -2, were identified as showing significant high expression in group 2 compared with group 1. Multivariate analysis demonstrated that clustering for mononuclear inflammatory cells was the most potent independent factor associated with distant relapse-free survival (group 2: 5.6 (3.5 -9.6), Po0.001). We identify a phenotype of mononuclear inflammatory cells infiltrating tumours, which is associated with the development of distant metastasis. Therefore, this finding suggests that these host inflammatory cells could be a possible target for inhibition of metastasis.

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“…It is a member of the TIMP family currently comprising four members (TIMP-1, -2, -3, and -4), is expressed by a wide range of cells, and is present in most tissues and body fluids (11,12). High levels of TIMP-1 mRNA as well as TIMP-1 protein have been found in several types of cancers including breast cancer, and this has been associated with a poor prognosis (13)(14)(15)(16)(17). That high levels of TIMP-1 predict a poor prognosis has been explained by at least two different models (4).…”

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confidence: 99%

“…TIMP-1 in complex with pro-MMP-9 (26) and with various activated MMPs and as uncomplexed TIMP-1. So far the prognostic value of only the total amount of TIMP-1 (uncomplexed TIMP-1 plus TIMP-1/MMP complexes) has been evaluated (13)(14)(15)(16)(17). In the case of other markers such as prostate-specific antigen it has been shown that specific fractions of the antigen carry useful clinical information (27), and we raised the hypothesis that this could also be the case for TIMP-1.…”

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confidence: 99%

Measurement of the Uncomplexed Fraction of Tissue Inhibitor of Metalloproteinases-1 in the Prognostic Evaluation of Primary Breast Cancer Patients*

Würtz¹,

Christensen

Schrohl³

et al. 2005

Molecular & Cellular Proteomics

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Several studies have demonstrated an association between high tumor tissue levels of total tissue inhibitor of metalloproteinases-1 (TIMP-1) and a poor prognosis of primary breast cancer patients. In the present study we investigated whether measurements of the uncomplexed fraction of TIMP-1 added prognostic information to that already obtained from total TIMP-1. We measured the uncomplexed fraction of TIMP-1, using a thoroughly validated ELISA specific for this fraction, in 341 tumor tissue extracts obtained from patients with primary breast cancer. These measurements were related to previously performed measurements of total TIMP-1 as well as to patient outcome. The observation time was 8.3 years (range, 7.3-11.3 years). During this period 136 patients died, and 153 patients experienced recurrence of disease. Cox regression analysis of recurrence-free survival (RFS) suggested that a score based on both uncomplexed and total TIMP-1, reflecting the tumor level of TIMP-1/MMP complexes, would be a more precise estimate of prognosis than total TIMP-1 alone. Univariate survival analysis showed a highly significant relationship between high values of the score and poor outcomes for RFS (p ‫؍‬ 0.0002; hazard ratio ‫؍‬ 2.7; 95% confidence interval, 1.5-4.8). Similar results were found for overall survival (p ‫؍‬ 0.0001; hazard ratio ‫؍‬ 3.3; 95% confidence interval, 1.8 -6.3). Multivariate analysis of RFS and overall survival demonstrated that the score was significant including the classical prognostic factors used in breast cancer (p < 0.0001). The present study raises the hypothesis that it is the tumor level of TIMP-1/MMP complexes (i.e. activated matrix metalloproteinases) rather than TIMP-1 itself that determines prognosis, supporting the use of the combined score and not only total TIMP-1 in stratification of breast cancer patients. Molecular & Cellular Proteomics 4:483-491, 2005.

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Enhanced mRNA expression of tissue inhibitor of metalloproteinase‐1 (TIMP‐1) in breast carcinomas is correlated with adverse prognosis

Cited by 78 publications

References 30 publications

Association of tissue inhibitor of metalloproteinases-1 and Ki67 in estrogen receptor positive breast cancer

Association of tissue inhibitor of metalloproteinases-1 and Ki67 in estrogen receptor positive breast cancer

Overexpression of matrix metalloproteinases and their inhibitors in mononuclear inflammatory cells in breast cancer correlates with metastasis-relapse

Measurement of the Uncomplexed Fraction of Tissue Inhibitor of Metalloproteinases-1 in the Prognostic Evaluation of Primary Breast Cancer Patients*

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