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Breast Cancer Research and Treatment

, Volume 98, Issue 1, pp 71–79 | Cite as

Abnormal ezrin localization is associated with clinicopathological features in invasive breast carcinomas

  • David Sarrió
  • Socorro María Rodríguez-Pinilla
  • Ana Dotor
  • Francisco Calero
  • David Hardisson
  • José Palacios
Preclinical study

Summary

The membrane-cytoskeleton crosslinker ezrin is associated with malignant progression and metastasis in human neoplasias. To study the role of ezrin in breast cancer, we first assessed ezrin expression in a panel of breast cancer cell lines by western blot and confocal microscopy. Western blot revealed no differences in total ezrin levels among these breast cell lines. However, immunofluorescence staining revealed that Estrogen receptor (ER)-positive, noninvasive and nontumorigenic cell lines concentrated ezrin at the apical surface, whereas invasive cell lines localized ezrin in motile structures (membrane ruffles and filopodia) but also had more diffuse cytoplasmic staining. We next studied ezrin expression in 509 breast carcinomas using tissue microarrays. Immunohistochemical staining for ezrin, p53, Ki-67, phospho-Akt, HER2, and hormonal receptors was performed. Ezrin staining in normal breast epithelium localized at the apical, but not lateral, cell surface, whereas, in most breast tumor cases (331, 70.3%), it localized in the cytoplasm. Complete membranous staining occurred in 89 (18.9%) samples, and apical staining was seen in 51 (10.8%) cases. There were significant positive associations between cytoplasmic ezrin localization and adverse tumor characteristics such as high grade, high level of Ki-67 expression, hormonal-receptor negativity, and lymph-node metastases. Apical ezrin staining was associated with favorable clinicopathological features and node-negative tumors. Membranous ezrin staining was associated with high grade, strong HER2 and p-Akt expression. In conclusion, the switch of ezrin localization from the apical membrane to either the complete membrane or to the cytoplasm is correlated with dedifferentiation and adverse features in invasive breast tumors and cancer cell lines.

Keywords

breast cancer ezrin ERM proteins tissue microarrrays 

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Notes

Acknowledgements

The authors thank Diego Megías (Biotechnology Programme, CNIO) and Ester Martín-Villar (CSIC, Madrid, Spain) for helping with confocal microscopy experiments. We are also grateful to Amancio Carnero (Experimental Therapeutics Programme, CNIO) for providing cell lines, and the CNIO Immunohistochemical Unit for expert technical assistance. David Sarrió (BEFI, 01/9132), and S. María Rodriguez-Pinilla are recipients of research grants from the Fondo de Investigación Sanitaria, Spain. Partially supported by grant SAF2004-08258-C02-01 to José Palacios.

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • David Sarrió
    • 1
  • Socorro María Rodríguez-Pinilla
    • 1
  • Ana Dotor
    • 2
  • Francisco Calero
    • 3
  • David Hardisson
    • 4
  • José Palacios
    • 1
    • 5
  1. 1.Breast and Gynaecological Cancer Group, Molecular Pathology ProgrammeCentro Nacional de Investigaciones Oncológicas (CNIO)MadridSpain
  2. 2.Spanish National Tumour Bank Network, Molecular Pathology Programme Centro Nacional de Investigaciones Oncológicas (CNIO)MadridSpain
  3. 3.Department of Obstetrics and Gynecology La Paz HospitalMadridSpain
  4. 4.Department of PathologyLa Paz HospitalMadridSpain
  5. 5.Programa de Patología MolecularCentro Nacional de Investigaciones Oncológicas (CNIO)MadridSpain

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