Skip to main content
Top
Published in: Annals of Surgical Oncology 8/2009

01-08-2009 | Breast Oncology

Extracellular Matrix 1 (ECM1) Expression Is a Novel Prognostic Marker for Poor Long-Term Survival in Breast Cancer: A Hospital-Based Cohort Study in Iowa

Authors: Geeta Lal, MD, MSc, Samad Hashimi, MD, Brian J. Smith, PhD, Charles F. Lynch, MD, PhD, Lurong Zhang, MD, PhD, Robert A. Robinson, MD, PhD, Ronald J. Weigel, MD, PhD

Published in: Annals of Surgical Oncology | Issue 8/2009

Login to get access

Abstract

Introduction

Previous work in a small, unselected series showed that up to 83% of breast carcinomas overexpress ECM1 by immunohistochemistry (IHC) and that tumors with lymph node metastases are more likely to be ECM1-positive. We sought to further evaluate ECM1 expression and its effect on prognosis in an unselected cohort of patients with breast cancer.

Methods

ECM1 expression was examined by IHC in 134 women diagnosed with invasive breast cancer between 1986 and 1989 and correlated with clinical parameters and outcomes, including disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) using Cox proportional hazards regression.

Results

During follow-up, 83 of 134 (66%) patients died. The median follow-up was 211 (range, 183–245) months for surviving patients. Based on a previously described cutoff of 10% staining, 47% of breast cancers were ECM1-positive. ECM1-positive tumors were associated with increasing patient age (P = 0.01). In multivariate analyses, while controlling for age, ER status, tumor grade, stage, and treatment, ECM1 expression emerged as a significant predictor of DSS (hazard ratios, 4.16 (P = 0.009) and 11.6 (P = 0.01) at 10 and 15 years, respectively) and DFS (hazard ratio, 3.08 (P = 0.03) at 15 years) with ECM1 overexpression predicting poorer survival.

Conclusions

ECM1 was overexpressed in approximately half of invasive breast carcinomas and is an important prognostic marker, particularly for predicting poorer DSS, with its predictive value increasing with time from diagnosis. Further work is needed to confirm these findings and determine whether ECM1 expression is predictive of response to specific therapy.
Literature
2.
go back to reference Proceedings of the 9th International Conference on Primary Therapy of Early Breast Cancer. 26–29 January 2005. St. Gallen, Switzerland. Breast. 2005;14:427–642. Proceedings of the 9th International Conference on Primary Therapy of Early Breast Cancer. 26–29 January 2005. St. Gallen, Switzerland. Breast. 2005;14:427–642.
3.
go back to reference Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet. 1998;351:1451–67.CrossRef Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet. 1998;351:1451–67.CrossRef
4.
go back to reference Diaz LK, Sneige N. Estrogen receptor analysis for breast cancer: current issues and keys to increasing testing accuracy. Adv Anat Pathol. 2005;12:10–9.PubMedCrossRef Diaz LK, Sneige N. Estrogen receptor analysis for breast cancer: current issues and keys to increasing testing accuracy. Adv Anat Pathol. 2005;12:10–9.PubMedCrossRef
5.
6.
go back to reference Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20:719–26.PubMedCrossRef Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20:719–26.PubMedCrossRef
7.
go back to reference Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.PubMedCrossRef Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.PubMedCrossRef
8.
go back to reference Jordan VC, Wolf MF, Mirecki DM, Whitford DA, Welshons WV. Hormone receptor assays: clinical usefulness in the management of carcinoma of the breast. Crit Rev Clin Lab Sci. 1988;26:97–152.PubMedCrossRef Jordan VC, Wolf MF, Mirecki DM, Whitford DA, Welshons WV. Hormone receptor assays: clinical usefulness in the management of carcinoma of the breast. Crit Rev Clin Lab Sci. 1988;26:97–152.PubMedCrossRef
9.
go back to reference Johnson MR, Wilkin DJ, Vos HL, Ortiz de Luna RI, Dehejia AM, Polymeropoulos MH, Francomano CA. Characterization of the human extracellular matrix protein 1 gene on chromosome 1q21. Matrix Biol. 1997;16:289–92.PubMedCrossRef Johnson MR, Wilkin DJ, Vos HL, Ortiz de Luna RI, Dehejia AM, Polymeropoulos MH, Francomano CA. Characterization of the human extracellular matrix protein 1 gene on chromosome 1q21. Matrix Biol. 1997;16:289–92.PubMedCrossRef
10.
go back to reference Smits P, Ni J, Feng P, Wauters J, Van Hul W, Boutaibi ME, et al. The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern, and chromosomal localization. Genomics. 1997;45:487–95.PubMedCrossRef Smits P, Ni J, Feng P, Wauters J, Van Hul W, Boutaibi ME, et al. The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern, and chromosomal localization. Genomics. 1997;45:487–95.PubMedCrossRef
11.
go back to reference Smits P, Poumay Y, Karperien M, et al. Differentiation-dependent alternative splicing and expression of the extracellular matrix protein 1 gene in human keratinocytes. J Invest Dermatol. 2000;114:718–24.PubMedCrossRef Smits P, Poumay Y, Karperien M, et al. Differentiation-dependent alternative splicing and expression of the extracellular matrix protein 1 gene in human keratinocytes. J Invest Dermatol. 2000;114:718–24.PubMedCrossRef
12.
go back to reference Sercu S, Zhang L, Merregaert J. The extracellular matrix protein 1: its molecular interaction and implication in tumor progression. Cancer Invest. 2008;26:375–84.PubMedCrossRef Sercu S, Zhang L, Merregaert J. The extracellular matrix protein 1: its molecular interaction and implication in tumor progression. Cancer Invest. 2008;26:375–84.PubMedCrossRef
13.
go back to reference Hamada T, McLean WH, Ramsay M, et al. Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (ECM1). Hum Mol Genet. 2002;11:833–40.PubMedCrossRef Hamada T, McLean WH, Ramsay M, et al. Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (ECM1). Hum Mol Genet. 2002;11:833–40.PubMedCrossRef
14.
go back to reference Han Z, Ni J, Smits P, et al. Extracellular matrix protein 1 (ECM1) has angiogenic properties and is expressed by breast tumor cells. Faseb J. 2001;15:988–94.PubMedCrossRef Han Z, Ni J, Smits P, et al. Extracellular matrix protein 1 (ECM1) has angiogenic properties and is expressed by breast tumor cells. Faseb J. 2001;15:988–94.PubMedCrossRef
15.
go back to reference Lal G, Padmanabha L, Nicholson R, et al. ECM1 expression in thyroid tumors—a comparison of real-time RT-PCR and IHC. J Surg Res. 2007. Lal G, Padmanabha L, Nicholson R, et al. ECM1 expression in thyroid tumors—a comparison of real-time RT-PCR and IHC. J Surg Res. 2007.
16.
go back to reference Kebebew E, Peng M, Reiff E, Duh QY, Clark OH, McMillan A. ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. Ann Surg. 2005;242:353–63.PubMed Kebebew E, Peng M, Reiff E, Duh QY, Clark OH, McMillan A. ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. Ann Surg. 2005;242:353–63.PubMed
17.
go back to reference Kebebew E, Peng M, Reiff E, McMillan A. Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms. Cancer. 2006;106:2592–7.PubMedCrossRef Kebebew E, Peng M, Reiff E, McMillan A. Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms. Cancer. 2006;106:2592–7.PubMedCrossRef
18.
go back to reference Wang L, Yu J, Ni J, et al. Extracellular matrix protein 1 (ECM1) is overexpressed in malignant epithelial tumors. Cancer Lett. 2003;200:57–67.PubMedCrossRef Wang L, Yu J, Ni J, et al. Extracellular matrix protein 1 (ECM1) is overexpressed in malignant epithelial tumors. Cancer Lett. 2003;200:57–67.PubMedCrossRef
19.
go back to reference Nessling M, Richter K, Schwaenen C, et al. Candidate genes in breast cancer revealed by microarray-based comparative genomic hybridization of archived tissue. Cancer Res. 2005;65:439–47.PubMed Nessling M, Richter K, Schwaenen C, et al. Candidate genes in breast cancer revealed by microarray-based comparative genomic hybridization of archived tissue. Cancer Res. 2005;65:439–47.PubMed
20.
go back to reference McPherson LA, Woodfield GW, Weigel RJ. AP2 transcription factors regulate expression of CRABPII in hormone responsive breast carcinoma. J Surg Res. 2007;138:71–8.PubMedCrossRef McPherson LA, Woodfield GW, Weigel RJ. AP2 transcription factors regulate expression of CRABPII in hormone responsive breast carcinoma. J Surg Res. 2007;138:71–8.PubMedCrossRef
21.
go back to reference Brewster AM, Hortobagyi GN, Broglio KR, et al. Residual risk of breast cancer recurrence 5 years after adjuvant therapy. J Natl Cancer Inst. 2008;100:1179–83.PubMedCrossRef Brewster AM, Hortobagyi GN, Broglio KR, et al. Residual risk of breast cancer recurrence 5 years after adjuvant therapy. J Natl Cancer Inst. 2008;100:1179–83.PubMedCrossRef
22.
go back to reference Pawlak G, Helfman DM. Cytoskeletal changes in cell transformation and tumorigenesis. Curr Opin Genet Dev. 2001;11:41–7.PubMedCrossRef Pawlak G, Helfman DM. Cytoskeletal changes in cell transformation and tumorigenesis. Curr Opin Genet Dev. 2001;11:41–7.PubMedCrossRef
23.
go back to reference Turner BC, Zhang J, Gumbs AA, et al. Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways. Cancer Res. 1998;58:5466–72.PubMed Turner BC, Zhang J, Gumbs AA, et al. Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways. Cancer Res. 1998;58:5466–72.PubMed
24.
go back to reference Pellikainen J, Naukkarinen A, Ropponen K, et al. Expression of HER2 and its association with AP-2 in breast cancer. Eur J Cancer. 2004;40:1485–95.PubMedCrossRef Pellikainen J, Naukkarinen A, Ropponen K, et al. Expression of HER2 and its association with AP-2 in breast cancer. Eur J Cancer. 2004;40:1485–95.PubMedCrossRef
25.
go back to reference Bosher JM, Totty NF, Hsuan JJ, Williams T, Hurst HC. A family of AP-2 proteins regulates c-erbB-2 expression in mammary carcinoma. Oncogene. 1996;13:1701–7.PubMed Bosher JM, Totty NF, Hsuan JJ, Williams T, Hurst HC. A family of AP-2 proteins regulates c-erbB-2 expression in mammary carcinoma. Oncogene. 1996;13:1701–7.PubMed
26.
go back to reference Bosher JM, Williams T, Hurst HC. The developmentally regulated transcription factor AP-2 is involved in c-erbB-2 overexpression in human mammary carcinoma. Proc Natl Acad Sci USA. 1995;92:744–7.PubMedCrossRef Bosher JM, Williams T, Hurst HC. The developmentally regulated transcription factor AP-2 is involved in c-erbB-2 overexpression in human mammary carcinoma. Proc Natl Acad Sci USA. 1995;92:744–7.PubMedCrossRef
27.
go back to reference Wang Y, Klijn JG, Zhang Y, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005;365:671–9.PubMed Wang Y, Klijn JG, Zhang Y, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005;365:671–9.PubMed
28.
go back to reference Sotiriou C, Wirapati P, Loi S, et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006;98:262–72.PubMedCrossRef Sotiriou C, Wirapati P, Loi S, et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006;98:262–72.PubMedCrossRef
30.
go back to reference Bergamaschi A, Tagliabue E, Sorlie T, et al. Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J Pathol. 2008;214:357–67.PubMedCrossRef Bergamaschi A, Tagliabue E, Sorlie T, et al. Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J Pathol. 2008;214:357–67.PubMedCrossRef
31.
go back to reference Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.PubMedCrossRef Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.PubMedCrossRef
32.
go back to reference Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.PubMedCrossRef Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.PubMedCrossRef
33.
go back to reference van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.PubMedCrossRef van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.PubMedCrossRef
34.
go back to reference Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRef Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRef
35.
go back to reference Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726–34.PubMedCrossRef Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726–34.PubMedCrossRef
Metadata
Title
Extracellular Matrix 1 (ECM1) Expression Is a Novel Prognostic Marker for Poor Long-Term Survival in Breast Cancer: A Hospital-Based Cohort Study in Iowa
Authors
Geeta Lal, MD, MSc
Samad Hashimi, MD
Brian J. Smith, PhD
Charles F. Lynch, MD, PhD
Lurong Zhang, MD, PhD
Robert A. Robinson, MD, PhD
Ronald J. Weigel, MD, PhD
Publication date
01-08-2009
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 8/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0533-2

Other articles of this Issue 8/2009

Annals of Surgical Oncology 8/2009 Go to the issue