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

Abstract

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.

• Authors: David Sarrió, Socorro María Rodríguez-Pinilla, Ana Dotor, Francisco Calero, David Hardisson, José Palacios
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 98 Issue 1 Pg. 71-9 (Jul 2006) ISSN: 0167-6806 [Print] Netherlands
• PMID: 16538541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytoskeletal Proteins
• Ki-67 Antigen
• Tubulin
• ezrin

Topics

• Breast Neoplasms (metabolism)
• Cell Line, Tumor
• Cell Membrane (metabolism)
• Cytoplasm (metabolism)
• Cytoskeletal Proteins (biosynthesis, chemistry)
• Cytoskeleton (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Ki-67 Antigen (biosynthesis)
• Lymphatic Metastasis
• Microscopy, Confocal
• Neoplasm Invasiveness
• Oligonucleotide Array Sequence Analysis
• Tubulin (chemistry)