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Abstract R etinoblastoma represents the most common cause of intraocular tumours in children, representing over 80% of cases under the age of 15 years (Balmer and Munier, 2001). It has the lowest median age of all childhood malignancies, approximately 15 months (Yeole and Advani, 2002). Sixty percent of retinoblastomas are unilateral; most of these forms are not hereditary and the median age at diagnosis is two years. However, 40% of retinoblastomas are bilateral with median age at diagnosis of one year. All bilateral and multifocal unilateral forms are hereditary (Aerts et al., 2006). Management of patients with retinoblastoma must take into account the various aspects of the disease: the visual risk, the possibly hereditary nature, the life-threatening risk. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is taken according to the histological risk factors (Aerts et al., 2006), which include: optic nerve and deep choroidal invasion, orbital extension, and metastatic disease (Li et al., 2012). CD24 is a glycosylphosphatidylinositol-anchored membrane protein (Schabath et al., 2006). It is expressed in hematopoietic cell subpopulations, especially B lymphocytes (Salamone et al., 2001). It is also present in certain epithelial cells such as keratinocytes and renal tubular epithelium (Baumann et al., 2005), and the developing brain (Schabath et al., 2006). CD24 is thought to function as an adhesion molecule. It is known to bind to P-selectin, a protein expressed on thrombin-activated platelets and endothelial cells, allowing adhesion of monocytes or neutrophils to them (Ju et al., 2011), and to L1, a member of the immunoglobulin superfamily that is expressed on neural and lymphoid cells (Baumann et al., 2005). It, also, has a role in stimulating proliferation and maturation of pre-B lymphocytes within the bone marrow (Salamone et al., 2001). An expanding body of literature points to a role for CD24 in the tumorigenesis and progression of a number of types of cancer including breast cancer, non–small cell lung carcinomas, epithelial ovarian, colorectal and prostate tumors, as well as B-cell lymphoma, renal cell carcinoma, small cell lung carcinoma, nasopharyngeal carcinoma, hepatocellular carcinoma, Merkel cell carcinoma, pancreatic carcinoma, glioma, tumours of neuroectodermal origin, bladder carcinoma, choriocarcinoma, and cholangiocarcinoma (Salamone et al., 2001; Baumann et al., 2005; Schabath et al., 2006; Li et al., 2012). It has been proposed that CD24-mediated binding to P-selectin on endothelial cells and platelets could favor metastasis (Schabath et al., 2006). Furthermore, CD24 expression increases tumor cell proliferation and also indirectly stimulates cell adhesion to fibronectin, collagens I and IV, and laminin. Moreover, CD24 expression supports rapid cell spreading and strongly induces cell motility and invasion (Baumann et al., 2005). To our knowledge, very few studies were performed to assess CD24 expression and its prognostic significance in retinoblastoma worldwide and no such studies were conducted in Egypt in particular, nor the middle-east region in general. The aim of this study was to evaluate the immunohistochemical expression of CD24 in retinoblastoma and to correlate it with different histopathological parameters aiming at identifying the potential prognostic significance of CD24 in retinoblastoma. This study included 33 cases of retinoblastoma, which were collected from the Pathology Department of Ain-Shams University Specialized Hospital and ElDemardash Hospital during the period from 2010-2015. The selected blocks were sectioned 5µm thick sections and immunostained using antihuman CD24 antibody. Semiquantitative assessment of immunostaining results followed by statistical analysis to correlate it with different clincopathological prognostic parameters was carried out. We found that CD24 is commonly overexpressed in retinoblastoma, as we observed CD24 immunoreactivity in all cases included in our study. Immunohistochemically determined CD24 expression is a potential marker of prognosis in this disease. It is increased in high-risk tumors compared to low-risk tumors and in extraocular retinoblastomas as compared to purely intraocular cases. A statistically significant difference was observed between low and high risk group’s CD24 expression in terms of intensity and extent. A statistically significant difference was also observed between CD24 expression in terms of extent as regards extraocular extension. Moreover, membranous-cytoplasmic CD24 staining pattern was strongly correlated with extraocular extension in retinoblastoma. The clinical implications of our findings include possible use of CD24 expression in enucleation specimens in a manner similar to high risk features in guiding postenucleation chemotherapy in retinoblastoma patients. Moreover, this expression in retinoblastoma, which is in part membranous, might be a target for therapeutic anti- CD24 antibodies but this point needs further studying. |