CD24 EXPRESSION IN RETINOBLASTOMA: POTENTIAL PROGNOSTIC ROLE

Abstract

SUMMARY 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).