Ezrin immunohistochemical expression in cartilaginous tumours: A useful tool for differential diagnosis between chondroblastic osteosarcoma and chondrosarcoma
Ezrin is a cytoskeleton linker protein that is actively involved in the metastatic process of cancer cells. We have recently reported that ezrin expression in conventional osteosarcoma was an independent prognostic factor for event-free survival and overall survival. In this work, ezrin expression was found in all histological subtypes. Especially cartilaginous areas in chondroblastic osteosarcomas were immunopositive for ezrin. We wanted to know if ezrin could be a useful diagnostic marker in bone pathology. We have searched for ezrin expression in 208 cartilaginous tumours by immunohistochemistry and in 16 chondroblastic osteosarcomas. All conventional chondrosarcomas, whatever their grade, were negative, while ten of 16 chondroblastic osteosarcomas were positive. In contrast, dedifferentiated (five of 14) and mesenchymal chondrosarcomas (five of ten) showed ezrin positivity. Some chondroblastomas and more rarely chondromyxoid fibromas also exhibited ezrin expression. These data suggest that ezrin is a useful immunohistochemical marker for differential diagnosis between chondroblastic osteosarcomas and conventional chondrosarcomas with a specificity of 100%. Ezrin expression in dedifferentiated and mesenchymal chondrosarcomas which are aggressive neoplasms resistant to conventional treatment means that ezrin could be a therapeutic target. Ezrin expression in chondroblastomas is more intriguing and requires further study to assess prognostic value.
Available from: Marcelo Brigido
- "Recently, Salas et al.  introduced Ezrin expression as a prognostic factor for the survival rate of patients with conventional osteosarcoma, correlating its expression with tumor progression. It was also shown that Ezrin is useful as an immunohistochemical marker to differentiate between chondroblastic osteosarcomas and conventional chondrosarcomas . However, other osteosarcoma markers are required to further characterize this complex, multifactorial neoplasia. "
[Show abstract] [Hide abstract]
ABSTRACT: Osteosarcoma, a highly malignant disease, is the most common primary bone tumor and is frequently found in children and adolescents. In order to isolate antibodies against osteosarcoma antigens, a combinatorial osteosarcoma Fab library displayed on the surface of phages was used. After three rounds of selection on the surface of tumor cells, several osteosarcoma-reactive Fabs were detected. From these Fabs, five were better characterized, and despite having differences in their VH (heavy chain variable domain) and Vkappa (kappa chain variable domain) regions, they all bound to a protein with the same molecular mass. Further analysis by cell ELISA and immunocytochemistry suggested that the Fabs recognize a membrane-associated tumor antigen expressed in higher amounts in neoplasic cells than in normal tissue. These results suggest that the human Fabs selected in this work are a valuable tool for the study of this neoplasia.
BioMed Research International 12/2009; 2009:157531. DOI:10.1155/2009/157531 · 2.71 Impact Factor
Available from: Martina Leopizzi
[Show abstract] [Hide abstract]
ABSTRACT: The survival of osteosarcoma patients is connected to metastasis. The ezrin expression is associated with the development of metastasis and poor outcome in osteosarcoma. Ezrin is present in the cytoplasm and after phosphorylation assumes an active form and links F-actin to the cell membrane. This study evaluated ezrin and phosphorylated ezrin at site Tyr354 and Thr567 expression and its subcellular localization in osteosarcoma. We studied 50 osteosarcoma patients (mean follow-up 9.8 years). Ezrin expression was assessed using immunohistochemical and immunofluorescence analysis on tissue microarray and cultured cells of human osteosarcoma 143B. The western blot analysis was carried out on cultured cells. The majority of osteosarcomas, showing cytoplasmic positivity for ezrin, phosphorylated and unphosphorylated, were associated with membranous and nuclear positivity for phosphorylated ezrin Thr567 and phosphorylated ezrin Tyr354, respectively. Ezrin expression was associated with high-grade osteosarcoma (P=0.04), with metastasis (P=0.04) and with tumors that developed metastasis (P=0.04); phosphorylated ezrin Thr567 expression was present mostly in tumors with metastasis (P=0.01) and in osteosarcomas that did not develop metastasis (P=0.002). The osteosarcoma patients with ezrin expression have a short survival. The cytoplasmic ezrin expression in osteosarcoma matches its role of membrane-cytoskeleton linker protein. The subcellular trafficking of ezrin is not blocked and it is linked to ezrin phosphorylation, also in cancer. The phosphorylated ezrin Tyr354 nuclear localization suggests its possible role as a nuclear factor in osteosarcoma. The phosphorylated ezrin Thr567 phosphorylation may not be necessary in osteosarcoma metastatic progression but it was modulated. The ezrin expression is associated with more aggressive osteosarcomas and with metastasis.
Modern Pathology 03/2010; 23(7):1012-20. DOI:10.1038/modpathol.2010.77 · 6.19 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Canine osteosarcoma (OS) is an aggressive tumour that accounts for approximately 90% of primary bone tumours in the dog. Although the standard treatments (including limb amputation/sparing, chemotherapy and palliative radiotherapy) have significantly increased survival rates, almost 90% of animals will eventually develop predominantly pulmonary metastases. Despite advances in various therapies, prognosis remains poor, with median survival times ranging from 3 months to 1 year and <20% of dogs survive for >2 years following diagnosis. Various clinical and epidemiological markers have facilitated decision-making with respect to therapy but no single molecular biomarker has been shown to enhance prediction of disease progression. The publication of the canine genome in 2005 raised the possibility of increasing understanding of the genetic mechanisms underpinning canine OS. This review explores the use of biomarkers within the multi-disciplinary management of dogs with OS, and highlights the few known, potential prognostic/predictive molecular markers including their potential value as 'bridging biomarkers' for human OS. Although high-throughput profiling of canine OS remains in its infancy, research within the next decade using leading-edge screening technologies has the potential to identify biomarkers that may enhance diagnostic and prognostic accuracy and result in more effective, individually tailored, treatment and management protocols for affected dogs.
The Veterinary Journal 07/2010; 185(1):28-35. DOI:10.1016/j.tvjl.2010.04.010 · 1.76 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.