Cytoplasmic ezrin and moesin correlate with poor survival in head and neck squamous cell carcinoma.
ABSTRACT Members of the 4.1 superfamily of proteins, including ezrin, moesin, merlin, and willin regulate many normal physiologic processes such as cellular shape, motility, and proliferation. In addition, they contribute both to tumor development and tumor progression. We reported previously that strong cytoplasmic ezrin expression was independently associated with poorer patient survival. One hundred and thirty-one histologically confirmed primary head and neck squamous cell carcinomas were examined prospectively for cancer progression and survival at a large health care center in the Bronx, NY, USA. Immunohistochemical analysis of ezrin, moesin, merlin, and willin expression in tissue microarray samples of primary head and neck squamous cell carcinoma revealed a significant association of increased cytoplasmic ezrin with poor cancer survival. Global RNA analyses suggest that cancers with high cytoplasmic ezrin have a more invasive phenotype. This study supports our previous findings associating cytoplasmic ezrin with more aggressive behavior and poorer outcome and indicates the need for a multi-institutional study to validate the use of cytoplasmic ezrin as a biomarker for treatment planning in head and neck squamous cell carcinoma.
[show abstract] [hide abstract]
ABSTRACT: The protein moesin is a member of a gene family consisting of talin, ezrin, radixin, protein 4.1., and merlin. Proteins of this family are associated to the submenbranous cytoskeleton. Using monoclonal antibody 38/87 directed against moesin in immunochemical analysis, the 78 kDa moesin protein was demonstrated in endothelial cells and in cells of carcinoma, mesothelioma and lymphoid origin. Moesin was metabolically labeled by [32P]orthophosphate and reacted with an antibody against phosphotyrosine. Moesin also contains carbohydrate residues as demonstrated by immunostainings of digoxigenin-labeled sugar residues. The antibody 38/87 in comparison to antisera against radixin and ezrin was applied in immunohistological stainings on various human tissues. As a prominent feature, moesin as strongly expressed in endothelium of vessels in contrast to radixin and ezrin. Moesin but not radixin was observed in T and B lymphocytes. Further, moesin was expressed in basal layers of squamous epithelium and glandular ducts and lymphocytes. Subcellular expression of moesin was studied on cultured human endothelial cells of umbilical cord veins and the mesothelioma cell line CH3LC by confocal laser scanning microscopy. In subconfluently growing cells moesin showed a characteristic expression on extending microspikes at the basal cell level. Moesin was coexpressed with actin in the cortical cytoskeleton and on microspikes but not in stress fibers. The differential cellular expression of moesin and its pronounced occurrence on microspikes of growing cells support the possibility that moesin is a protein involved in plasma membrane-cytoskeleton interactions in specialized tissues.European Journal of Cell Biology 08/1995; 67(3):189-98. · 2.81 Impact Factor
Article: Clinical implications of expression of ETS-1 related to angiogenesis in metastatic lesions of ovarian cancers.[show abstract] [hide abstract]
ABSTRACT: ETS-1 has been identified as a proto-oncogene and a transcription factor for tumor angiogenesis, which is essential for the growth, invasion and metastasis of solid tumors. The aim is to investigate the clinical implications of ETS-1 expression in peritoneal metastatic lesions of ovarian cancers. In primary tumors and peritoneal metastatic lesions from 30 patients with stage III ovarian cancers, ETS-1 histoscores and ets-1 mRNA levels were determined by immunohistochemistry and competitive RT-PCR-Southern blot analysis using recombinant RNA, respectively. Immunohistochemical staining revealed that ETS-1 was expressed in the cancer cells and vascular endothelial cells. ETS-1 histoscores in the endothelial cells and ets-1 mRNA levels were significantly (p < 0.05) increased in 20 of 30 peritoneal metastatic lesions of ovarian cancers. There was a significant correlation between microvessel counts (MVCs) and ETS-1 histoscores in the endothelial cells (p < 0.001) and between MVCs and ets-1 mRNA levels in the primary tumor and the peritoneal metastatic lesion of ovarian cancers (p < 0.001). Furthermore, the 24-month survival rate of patients with significantly increased ets-1 mRNA level (2/20, 10%) was significantly (p < 0.01) lower than that of patients with no change in the level (6/10, 60%) from the primary tumor to the peritoneal metastatic lesion. ETS-1 might be associated with peritoneal metastasis dominantly as an angiogenic mediator and additionally as an oncogene product to activate tumor invasion in ovarian cancers.Oncology 01/2004; 66(5):420-8. · 2.27 Impact Factor