Skip to main content

Advertisement

Log in

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

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. www.seer.cancer.gov.

  2. 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. Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet. 1998;351:1451–67.

    Article  Google Scholar 

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. Duffy MJ. Predictive markers in breast and other cancers: a review. Clin Chem. 2005;51:494–503.

    Article  PubMed  CAS  Google Scholar 

  6. 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.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. 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. 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  Google Scholar 

  17. Kebebew E, Peng M, Reiff E, McMillan A. Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms. Cancer. 2006;106:2592–7.

    Article  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  CAS  Google Scholar 

  19. 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  CAS  Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. Pawlak G, Helfman DM. Cytoskeletal changes in cell transformation and tumorigenesis. Curr Opin Genet Dev. 2001;11:41–7.

    Article  PubMed  CAS  Google Scholar 

  23. 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  CAS  Google Scholar 

  24. 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.

    Article  PubMed  CAS  Google Scholar 

  25. 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  CAS  Google Scholar 

  26. 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.

    Article  PubMed  CAS  Google Scholar 

  27. 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  CAS  Google Scholar 

  28. 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.

    Article  PubMed  CAS  Google Scholar 

  29. http://www.oncomine.org/.

  30. 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.

    Article  PubMed  CAS  Google Scholar 

  31. 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.

    Article  PubMed  CAS  Google Scholar 

  32. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  Google Scholar 

  34. 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.

    Article  PubMed  CAS  Google Scholar 

  35. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by an Association of Women Surgeons–Genomic Health fellowship to GL. The authors thank Ms. Deb Schulte for expert assistance with the Iowa Cancer Registry database and Thomas Weinzerl for assistance with figures.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Geeta Lal MD, MSc.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lal, G., Hashimi, S., Smith, B.J. et al. 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. Ann Surg Oncol 16, 2280–2287 (2009). https://doi.org/10.1245/s10434-009-0533-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-009-0533-2

Keywords

Navigation