Assessment of Glypican 3 as a Predictive Marker in Colorectal Cancer Patients

Colorectal cancer (CRC) is the third most common malignancy and the fourth most prominent cause of cancer-related deaths worldwide. Also it is the 7th commonest cancer in Egypt, representing 3.47% of male cancers and 3% of female cancers.The Glypicans , a family of proteins classified as HSPGs (heparan sulfate proteoglycan) , have been shown to interact with a number of growth factors and modulate growth factor activity and are linked to the xtracellular side of cell membrane by a glycosylphosphatidylinositol (GPI) anchor . Members of this large family of transmembrane proteins have been identified in both mammals and drosophila: 6 glypicans (GPC-1 through GPC-6) in mammals, and two others in the fly .Glypican-3 (GPC3) as one of this family is a protein of about 70 kD . It has multiple sugar chains and heparan sulfate modification sites . These proteins (Glypicans) participate in organ development by modulating extracellular growth signals and morphogen gradient formation, and are involved in human overgrowth and skeletal dysplasia problems .In some cancers, they are highly expressed, associated with tumorigenesis, and regulating angiogenesis for cancer progression and invasion . Abnormal expression of glypicans has been noted in multiple types of cancer. For examples, GPC-1 expression was found to be increased in breast cancer tissues and ovarian malignant tumors .GPC-2 is associated with neuroblastoma .Expression of GPC-3 was found in high-grade urothelial carcinoma and also reported in some non-CNS tumors of the brain.There have been several reports about the clinical usefulness of the N-terminal form of GPC3. Enzyme-linked immunosorbent assay methods capable of detecting the N-terminal form of GPC3 . A study of colorectal cancer tissue speciment shows a correlation between expression of GPC3 with the clinicopathologic variables such as the level of differentiation, GPC3 was found to be expressed in ( 42.8% ) of the well-differentiated tumors, and (50%) of the moderately differentiated tumors, (75%) of the moderately and poorly differentiated tumors .Therefore, it was found that the expression of GPC3 was correlated with the pathological grade of the tumors .