Advertisement

Tumor Biology

, Volume 35, Issue 9, pp 8849–8860 | Cite as

The diagnostic, predictive, and prognostic role of serum epithelial cell adhesion molecule (EpCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in breast cancer

  • S. KarabulutEmail author
  • F. Tas
  • D. Tastekin
  • M. Karabulut
  • C. T. Yasasever
  • R. Ciftci
  • M. Güveli
  • M. Fayda
  • S. Vatansever
  • M. Serilmez
  • R. Disci
  • A. Aydıner
Research Article

Abstract

The purpose of this study was to determine the clinical significance of vascular cell adhesion molecule-1 (VCAM-1) and epithelial cell adhesion molecule (EpCAM) in breast cancer (BC) patients. Ninety-six BC patients and 30 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich (enzyme-linked immunosorbent assay (ELISA)). The median age at diagnosis was 48 years (range 29–80 years). Majority of the patients (71 %) had luminal subtype, and 38.5 % had metastatic disease. Twenty-nine (30 %) patients showed tumor progression, and 20 (21 %) patients died during follow-up. Median progression-free survival (PFS) and overall survival (OS) were 8.6 ± 1.7 and 35.5 ± 1.5 months, respectively. The baseline serum EpCAM levels of the patients were significantly higher than those of the controls (p < 0.001). There was no significant difference in the serum levels of VCAM-1 between the patients and controls (p = 0.47). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p > 0.05). Patients with HER-2-positive and triple-negative tumors had significantly poorer PFS (p = 0.04 and p = 0.001, respectively), while metastatic disease and chemotherapy unresponsiveness had significantly adverse effect on OS analysis (p < 0.001 and p < 0.001, respectively). Neither serum VCAM-1 levels nor serum EpCAM levels were identified to have a prognostic role on either PFS or OS (VCAM-1 p = 0.76 and p = 0.32; EpCAM p = 0.16 and p = 0.69, respectively). Even though any predictive or prognostic role could not be determined for both markers, serum levels of EpCAM were found to have diagnostic value in BC patients.

Keywords

EpCAM VCAM-1 Serum Breast cancer 

Notes

Conflicts of interest

None

Funding

No funding source

References

  1. 1.
    Saadatmand S, Kruijf EM, Sajet A, Dekker-Ensink NG, van Nes JG, Putter H, et al. Expression of cell adhesion molecules and prognosis in breast cancer. Br J Surg. 2013;100(2):252–60. doi: 10.1002/bjs.8980.CrossRefPubMedGoogle Scholar
  2. 2.
    Charalabopoulos K, Papalimneou V, Charalabopoulos A. Adhesion molecules in lung cancer. Exp Oncol. 2003;25:16–21.Google Scholar
  3. 3.
    Baeuerle P, Gires O. EpCAM (CD326) finding its role in cancer. Br J Cancer. 2007;96:417–23. doi: 10.1038/sj.bjc.6603494.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Went P, Vasei M, Bubendorf L, Terracciano L, Tornillo L, Riede U, et al. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br J Cancer. 2006;94:128–35. doi: 10.1038/sj.bjc.6602924.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Spizzo G, Obrist P, Ensinger C, Theurl I, Dünser M, Ramoni A, et al. Prognostic significance of Ep-CAM and Her-2/neu overexpression in invasive breast cancer. Int J Cancer. 2002;98:883–8. doi: 10.1002/ijc.10270.CrossRefPubMedGoogle Scholar
  6. 6.
    Osta WA, Chen Y, Mikhitarian K, Mitas M, Salem M, Hannun YA, et al. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res. 2004;64:5818–24. doi: 10.1158/0008-5472.CAN-04-0754.CrossRefPubMedGoogle Scholar
  7. 7.
    Maetzel D, Denzel S, Mack B, Canis M, Went P, Benk M, et al. Nuclear signaling by tumour-associated antigen EpCAM. Nat Cell Biol. 2009;11:162–71. doi: 10.1038/ncb1824.CrossRefPubMedGoogle Scholar
  8. 8.
    Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene. 2004;23:5748–58. doi: 10.1038/sj.onc.1207610.CrossRefPubMedGoogle Scholar
  9. 9.
    Schmidt DS, Klingbeil P, Schnolzer M, Zoller M. CD44 variant isoforms associated with tetraspanins and EpCAM. Exp Cell Res. 2004;297:329–47. doi: 10.1016/j.yexcr.2004.02.023.CrossRefPubMedGoogle Scholar
  10. 10.
    Patriarca C, Macchi RM, Marschner AK, Mellstedt H. Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer Treat Rev. 2012;38:68–75. doi: 10.1016/j.ctrv.2011.04.002.CrossRefPubMedGoogle Scholar
  11. 11.
    Cimino A, Halushka M, Illei P, Wu X, Sukumar S, Argani P. Epithelial cell adhesionmolecule (EpCAM) is overexpressed in breast cancer metastases. Breast Cancer Res Treat. 2010;123(3):701–8. doi: 10.1007/s10549-009-0671-z.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Königsberg R, Obermayr E, Bises G, Pfeiler G, Gneist M, Wrba F, et al. Detection of EpCAM positive and negative circulating tumor cells in metastatic breast cancer patients. Acta Oncol. 2011;50(5):700–10. doi: 10.3109/0284186X.2010.549151.CrossRefPubMedGoogle Scholar
  13. 13.
    Kim Y, Kim HS, Cui ZY, Lee HS, Ahn JS, Park CK, et al. Clinicopathological implications of EpCAM expression in adenocarcinoma of the lung. Anticancer Res. 2009;29:1817–22.PubMedGoogle Scholar
  14. 14.
    Gastl G, Spizzo G, Obrist P, Dünser M, Mikuz G. EpCAM overexpression in breast cancer as a predictor of survival. Lancet. 2000;356(9246):1981–2. doi: 10.1016/S0140-6736(00)03312-2.CrossRefPubMedGoogle Scholar
  15. 15.
    Spizzo G, Went P, Dirnhofer S, Obrist P, Simon R, Spichtin H, et al. High Ep-CAM expression is associated with poor prognosis in node-positive breast cancer. Breast Cancer Res Treat. 2004;86:207–13.CrossRefPubMedGoogle Scholar
  16. 16.
    Soysal SD, Muenst S, Barbie T, Fleming T, Gao F, Spizzo G, et al. EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2(+), basal-like, and HER2 intrinsic subtypes of breast cancer. Br J Cancer. 2013;108(7):1480–7. doi: 10.1038/bjc.2013.80.PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Agboola AJ, Paish EC, Rakha EA, Powe DG, Macmillan RD, Ellis IO, et al. EpCAM expression is an indicator of recurrence in basal-like breast cancer. Breast Cancer Res Treat. 2012;133(2):575–82. doi: 10.1007/s10549-011-1813-7.CrossRefPubMedGoogle Scholar
  18. 18.
    Schmidt M, Scheulen ME, Dittrich C, Obrist P, Marschner N, Dirix L, et al. An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer. Ann Oncol. 2010;21:275–82. doi: 10.1093/annonc/mdp314.CrossRefPubMedGoogle Scholar
  19. 19.
    Münz M, Murr A, Kvesic M, Rau D, Mangold S, Pflanz S, et al. Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies. Cancer Cell Int. 2010;10:44. doi: 10.1186/1475-2867-10-44.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Heiss MM, Murawa P, Koralewski P, Kutarska E, Kolesnik OO, Ivanchenko VV, et al. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer. 2010;127(9):2209–21.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G, et al. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989;59:1203–11. doi: 10.1016/0092-8674(89)90775-7.CrossRefPubMedGoogle Scholar
  22. 22.
    Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler ME, et al. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell. 1990;60:577–84. doi: 10.1016/0092-8674(90)90661-W.CrossRefPubMedGoogle Scholar
  23. 23.
    Chen Q, Zhang XH, Massague J. Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell. 2011;20(4):538–49. doi: 10.1016/j.ccr.2011.08.025.PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Koch AE, Halloran MM, Haskell CJ, Shah MR, Polverini PJ. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature. 1995;376:517–9. doi: 10.1038/376517a0.CrossRefPubMedGoogle Scholar
  25. 25.
    Minn AJ, Gupta GP, Padua D, Bos P, Nguyen DX, Nuyten D, et al. Lung metastasis genes couple breast tumor size and metastatic spread. Proc Natl Acad Sci U S A. 2007;104:6740–5. doi: 10.1073/pnas.0701138104.PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Banks RE, Gearing AJ, Hemingway IK, Norfolk DR, Perren TJ, Selby PJ. Circulating intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in human malignancies. Br J Cancer. 1993;68(1):122–4.PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    O’Hanlon DM, Fitzsimons H, Lynch J, Tormey S, Malone C, Given HF. Soluble adhesion molecules (E-selectin, ICAM-1 and VCAM-1) in breast carcinoma. Eur J Cancer. 2002;38(17):2252–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Silva HC, Garcao F, Coutinho EC, De Oliveira CF, Regateiro FJ. Soluble VCAM-1 and E-selectin in breast cancer: relationship with staging and with the detection of circulating cancer cells. Neoplasma. 2006;53(6):538–43.PubMedGoogle Scholar
  29. 29.
    Chen Q, Massagué J. Molecular pathways: VCAM-1 as a potential therapeutic target in metastasis. Clin Cancer Res. 2012;18(20):5520–5. doi: 10.1158/1078-0432.CCR-11-2904.PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Byrne GJ, Ghellal A, Iddon J, Blann AD, Venizelos V, Kumar S, et al. Serum soluble vascular cell adhesion molecule-1: role as a surrogate marker of angiogenesis. Natl Cancer Inst. 2000;92(16):1329–36. doi: 10.1093/jnci/92.16.1329.CrossRefGoogle Scholar
  31. 31.
    Giannoulis K, Angouridaki C, Fountzilas G, Papapolychroniadis C, Giannoulis E, Gamvros O. Serum concentrations of soluble ICAM-1 and VCAM-1 in patients with colorectal cancer. Clinical implications. Tech Coloproctol. 2004;8(1):65–7. doi: 10.1007/s10151-004-0115-7.CrossRefGoogle Scholar
  32. 32.
    Velikova G, Banks RE, Gearing A, Hemingway I, Forbes MA, Preston SR, et al. Circulating soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with gastric cancer. Br J Cancer. 1997;76(11):1398–404.PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics. CA Cancer J Clin. 2005;5:74–108.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • S. Karabulut
    • 1
    Email author
  • F. Tas
    • 1
  • D. Tastekin
    • 1
  • M. Karabulut
    • 2
  • C. T. Yasasever
    • 3
  • R. Ciftci
    • 1
  • M. Güveli
    • 4
  • M. Fayda
    • 4
  • S. Vatansever
    • 1
  • M. Serilmez
    • 3
  • R. Disci
    • 5
  • A. Aydıner
    • 1
  1. 1.Department of Medical Oncology, Oncology InstituteIstanbul UniversityIstanbulTurkey
  2. 2.Department of General SurgeryIstanbul Bakırköy Dr. Sadi Konuk Education and Research HospitalIstanbulTurkey
  3. 3.Department of Basic Oncology, Oncology InstituteIstanbul UniversityIstanbulTurkey
  4. 4.Department of Radiation Oncology, Oncology InstituteIstanbul UniversityIstanbulTurkey
  5. 5.Department of Biostatistics and Epidemiology, Institute of OncologyIstanbul UniversityIstanbulTurkey

Personalised recommendations