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MMP-1 Expression Has An Independent Prognostic Value In Breast Cancer

Pia Boström, M. Söderström, T. Vahlberg, K. Söderström, P. Roberts, O. Carpén, P. Hirsimäki
Published 2011 · Medicine

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AbstractBackgroundBreast cancer consists of a variety of tumours, which differ by their morphological features, molecular characteristics and outcome. Well-known prognostic factors, e.g. tumour grade and size, Ki-67, hormone receptor status, HER2 expression, lymph node status and patient age have been traditionally related to prognosis. Although the conventional prognostic markers are reliable in general, better markers to predict the outcome of an individual tumour are needed.Matrix metalloproteinase-1 (MMP-1) expression has been reported to inversely correlate with survival in advanced cancers. In breast cancer MMP-1 is often upregulated, especially in basal-type breast tumours. The purpose of this retrospective study was to analyse MMP-1 expression in breast cancer cells and in cancer associated stromal cells and to correlate the results with traditional prognostic factors including p53 and bcl-2, as well as to patient survival in breast cancer subtypes.MethodsImmunohistochemical analysis of MMP-1, ER, PR, Ki-67, HER2, bcl-2, p53 and CK5/6 expression was performed on 125 breast cancers. Statistical analyses were carried out using Kruskal-Wallis and Mann-Whitney -tests. In pairwise comparison Bonferroni-adjustment was applied. Correlations were calculated using Spearman rank-order correlation coefficients. Kaplan-Meier survival analyses were carried out to compare breast cancer-specific survival curves. Factors significantly associated with disease-specific survival in univariate models were included in multivariate stepwise.ResultsPositive correlations were found between tumour grade and MMP-1 expression in tumour cells and in stromal cells. P53 positivity significantly correlated with MMP-1 expression in tumour cells, whereas HER2 expression correlated with MMP-1 both in tumour cells and stromal cells. MMP-1 expression in stromal cells showed a significant association with luminal A and luminal B, HER2 overexpressing and triple-negative breast cancer subtypes.ConclusionsThe most important finding of this study was the independent prognostic value of MMP-1 as well as Ki-67 and bcl-2 expression in tumour cells. Our study showed also that both tumoural and stromal MMP-1 expression is associated with breast tumour progression and poor prognosis. A significant difference of MMP-1 expression by cancer associated stromal cells in luminal A, luminal B and triple-negative breast cancer classes was also demonstrated. Please see related commentary articlehttp://www.biomedcentral.com/1741-7015/9/95
This paper references
10.1186/bcr65
Metalloproteinases: role in breast carcinogenesis, invasion and metastasis
M. Duffy (2000)
10.1073/pnas.191367098
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
T. Sørlie (2001)
10.1007/s10549-008-0085-3
Matrix metalloproteinase-1 promotes breast cancer angiogenesis and osteolysis in a novel in vivo model
S. Eck (2008)
WHO Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs.Edited
P Ellis (2003)
10.1007/s10549-005-9042-6
Polymorphisms of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP-9 in breast cancer
K. Przybyłowska (2005)
10.1038/sj.bjc.6603666
Study of matrix metalloproteinases and their inhibitors in breast cancer
F. Vizoso (2007)
10.1007/s10549-010-1294-0
Current evidence on the relationship between four polymorphisms in the matrix metalloproteinases (MMP) gene and breast cancer risk: a meta-analysis
P. Zhou (2010)
10.1007/s10549-007-9556-1
An overview of prognostic factors for long-term survivors of breast cancer
I. Soerjomataram (2007)
10.1111/j.1365-2613.2010.00709.x
Comparative study of the expression of metalloproteases and their inhibitors in different localizations within primary tumours and in metastatic lymph nodes of breast cancer
M. J. García (2010)
10.1038/nrc745
New functions for the matrix metalloproteinases in cancer progression
M. Egeblad (2002)
Interstitial collagenases as markers of tumor progression.
C. Brinckerhoff (2000)
10.1038/35021093
Molecular portraits of human breast tumours
C. Perou (2000)
10.1186/1756-0500-2-140
Analysis of cyclins A, B1, D1 and E in breast cancer in relation to tumour grade and other prognostic factors
Pia Boström (2009)
10.1016/J.CARDIORES.2005.12.002
Structure and function of matrix metalloproteinases and TIMPs.
H. Nagase (2006)
Garcia-Muniz JL: Study of matrix metalloproteinases and their inhibitors in breast cancer
FJ Vizoso (2007)
10.1038/nature03799
Genes that mediate breast cancer metastasis to lung
A. Minn (2005)
10.1186/1471-2407-8-149
Androgen receptor expresion in breast cancer: Relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors
L. González (2007)
10.1007/s10555-006-7886-9
Matrix metalloproteinases and tumor metastasis
E. Deryugina (2006)
Polymorphismus of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP9 in breast cancer
K Przybylowska (2006)
WHO Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs
P Ellis (2003)
10.1016/J.CHEMBIOL.2006.01.012
Design and characterization of a metalloproteinase inhibitor-tethered resin for the detection of active MMPs in biological samples.
D. Hesek (2006)
10.1016/J.JSS.2007.05.032
High MMP-1 mRNA expression is a risk factor for disease-free and overall survivals in patients with invasive breast carcinoma.
S. Cheng (2008)
Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response.
K. Heppner (1996)
10.1016/S0092-8674(00)81683-9
The Hallmarks of Cancer
D. Hanahan (2000)
10.1016/S1040-8428(99)00034-7
Pathological prognostic factors in breast cancer.
C. Elston (1999)
Androgen receptor expression in breast cancer: Relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors
L González (2008)
Pathology and Genetics of Tumours of the Breast and Female Genital Organs
F. Tavassoli (2003)
10.1007/s00432-009-0721-2
Expression of metalloproteases and their inhibitors in different histological types of breast cancer
J. M. del Casar (2009)
10.1016/s0889-857x(05)70086-7
Women's health.
G. L. Lautenbach (1999)
10.1016/j.humpath.2008.12.022
Expression and prognostic significance of metalloproteases and their inhibitors in luminal A and basal-like phenotypes of breast carcinoma.
L. González (2009)
10.1186/1471-2407-9-188
Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature
Andrea Köhrmann (2008)
10.1093/annonc/mdn180
Matrix metalloproteinase expression and outcome in patients with breast cancer: analysis of a published database.
P. McGowan (2008)
10.1136/mp.55.5.300
Expression of proteinases and inhibitors in human breast cancer progression and survival
E. Baker (2002)
10.1126/SCIENCE.1067100
Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations
L. Coussens (2002)
Bcl-2 protein expression and long-term survival in breast cancer.
H. Joensuu (1994)
10.1093/ANNONC/MDL147
Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy.
V. Malamou-Mitsi (2006)
10.1200/JCO.2009.23.5556
Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer.
R. Roy (2009)
10.1188/08.CJON.861-863
Triple-negative breast cancer.
Debra L Winkeljohn (2008)
Polymorphismus of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP9 in breast cancer
K Przybylowska (2006)
Børresen-Dale A-L: Gene expression patterns of breast carcinomas distuinguish tumor subclasses with clinical implications
T Sørlie (2001)
10.1016/S0046-8177(99)90120-X
Matrix metalloproteinase-1 and -3 in breast cancer: correlation with progesterone receptors and other clinicopathologic features.
L. Nakopoulou (1999)
10.1002/ijc.10329
Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets
P. Vihinen (2002)
Bcl-2 Protein Expression and LongTerm Survival in Breast Cancer
H Joensuu (1994)
Bcl-2 expression in breast cancer: a comparative study at the mRNA and protein level.
F. Martínez-Arribas (2007)
10.1111/j.1365-2559.1991.tb00229.x
pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long‐term follow‐up
C. Elston (1991)
O’Higgins N: Metalloproteinases: role in breast carcinogenesis, invasion and metastasis
M Duffy (2000)



This paper is referenced by
THE PARACASPASE MALT1 IS A CRITICAL MEDIATOR OF PAR1-DRIVEN NF-κB ACTIVATION AND TUMOR METASTASIS
J. McAuley (2017)
10.1038/cddiscovery.2017.36
Nuclear matrix metalloproteinases: functions resemble the evolution from the intracellular to the extracellular compartment
Yingqiu Xie (2017)
10.1016/j.matbio.2016.05.003
Estrogen receptor beta modulates breast cancer cells functional properties, signaling and expression of matrix molecules.
Zoi Piperigkou (2016)
10.1038/s41416-018-0056-3
WSB-1 regulates the metastatic potential of hormone receptor negative breast cancer
Flore-Anne Poujade (2018)
10.1002/jcla.21764
Soluble Expression of Bladder Cancer Biomarker Matrix Metalloproteinase 1
Xuefei Jin (2015)
10.1186/1471-2407-14-472
Matrix metalloproteinase 1 and circulating tumor cells in early breast cancer
Z. Čierna (2014)
10.1074/jbc.M116.715797
Activation of Epidermal Growth Factor Receptor/p38/Hypoxia-inducible Factor-1α Is Pivotal for Angiogenesis and Tumorigenesis of Malignantly Transformed Cells Induced by Hexavalent Chromium*
D. Kim (2016)
10.1002/9781118772287.CH10
MMPs in Biology and Medicine
Di Jia (2015)
10.1007/s10549-012-2308-x
Plasma matrix metalloproteinases and postmenopausal breast cancer risk: a nested case–control study in the Multiethnic Cohort study
Y. Kim (2012)
10.3390/ijms12117445
gef Gene Expression in MCF-7 Breast Cancer Cells is Associated with a Better Prognosis and Induction of Apoptosis by p53-Mediated Signaling Pathway
H. Boulaiz (2011)
10.1016/j.matbio.2015.02.008
Estrogen receptor alpha mediates epithelial to mesenchymal transition, expression of specific matrix effectors and functional properties of breast cancer cells.
Panagiotis Bouris (2015)
10.1007/s10552-014-0462-7
Plasma matrix metalloproteinase 1, 3, and 7 levels and breast cancer risk in the Nurses’ Health Study
Sarah A. Aroner (2014)
10.2174/1566524017666170807144946
Gene Expression Meta-Analysis of Potential Metastatic Breast Cancer Markers
R. Bell (2017)
10.1371/journal.pone.0135544
Overexpression of MMP Family Members Functions as Prognostic Biomarker for Breast Cancer Patients: A Systematic Review and Meta-Analysis
F. Ren (2015)
10.1016/j.ejcb.2014.10.001
Tumor necrosis factor-α-accelerated degradation of type I collagen in human skin is associated with elevated matrix metalloproteinase (MMP)-1 and MMP-3 ex vivo
M. Ågren (2015)
10.3109/1354750X.2012.678885
Low serum MMP-1 in breast cancer: a negative prognostic factor?
A. Kulić (2012)
10.1074/jbc.M112.356303
Matrix Metalloprotease-1a Promotes Tumorigenesis and Metastasis*
C. Foley (2012)
10.1016/j.canlet.2015.02.018
Cancer-associated fibroblasts: a multifaceted driver of breast cancer progression.
Haojun Luo (2015)
10.3892/OL.2019.10669
An integrated bioinformatics analysis of potential therapeutic targets among matrix metalloproteinases in breast cancer
Haiqun Xia (2019)
10.5603/NJO.2014.0085
Importance and usefulness of diagnostic metaloproteinases in breast cancer
Ilona Zaręba (2015)
Comparative Analysis of NLS Sequence Suggests the Evolutionary Origin of Nuclear Matrix Metalloproteinase 7 during Cancer Evolution
D. Abdukhakimova (2016)
10.1155/2014/839094
The Complex Interaction of Matrix Metalloproteinases in the Migration of Cancer Cells through Breast Tissue Stroma
K. J. Davies (2014)
The effect of intense pulsed light treatment on the expression of transforming growth factor-β in acne vulgaris
M. M. Ali (2012)
10.3390/cancers12082273
Verification of Saliva Matrix Metalloproteinase-1 as a Strong Diagnostic Marker of Oral Cavity Cancer
Ya-Ting Chang (2020)
10.1083/jcb.201501034
The source of matrix-degrading enzymes in human cancer: Problems of research reproducibility and possible solutions
Daniel H. Madsen (2015)
10.1186/s40064-016-3734-8
The effects for PM2.5 exposure on non-small-cell lung cancer induced motility and proliferation
B. Yang (2016)
2012 Landes Bioscience. Do not distribute. Why the stroma matters in breast cancer Insights into breast cancer patient outcomes through the examination of stromal biomarkers
M. Conklin (2012)
10.1007/s11306-014-0723-1
Metabolomic and proteomic analysis of breast cancer patient samples suggests that glutamate and 12-HETE in combination with CA15-3 may be useful biomarkers reflecting tumour burden
P. Dowling (2014)
10.1007/s12307-012-0121-z
Transcription Factor Networks in Invasion-Promoting Breast Carcinoma-Associated Fibroblasts
A. Siletz (2012)
10.1007/s11684-016-0431-5
Breast cancer-associated fibroblasts: their roles in tumor initiation, progression and clinical applications
Aixiu Qiao (2016)
10.1016/j.semcancer.2017.11.008
Matrix Metalloproteinases: A challenging paradigm of cancer management.
Ali Alaseem (2019)
10.4161/cam.20567
Why the stroma matters in breast cancer
M. Conklin (2012)
See more
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