Glypican-3 expression in primary and metastatic neuroblastoma

Glypican-3 is an oncofetal protein found to be overexpressed in different types of tumours, such as hepatocellular carcinoma, malignant melanoma, squamous cell carcinoma of the lungs and testicular yolk sac tumour. Glypican-3 is currently emerging as a tumour marker and/or potential target for therapy of many cancers. However, there are limited studies looking for glypican-3 expression in neuroblastoma, with some evidence for loss of expression. Therefore, we sought to investigate glypican-3 expression in primary and metastatic neuroblastoma and to explore its potential as marker and/or target for development of new therapy for neuroblastoma. A total of 31 archived tissue specimens of neuroblastoma were subjected to immunohistochemical staining using a monoclonal antibody specific for glypican-3. Glypican-3 expression was compared with clinical and histological characteristics for each patient. Immunohistochemical analysis revealed for the first time overexpression of glypican-3 in 33% of neuroblastoma tumours. Its overexpression was surprisingly more predominant in metastatic tumours (71%) than in primary tumours. Glypican-3 expression was significantly correlated with disease clinical stages (P ≤ 0.05). It was more frequently expressed in the majority of stage 4s patients and connoted poor disease prognosis. On this basis, the biological functions and molecular mechanisms underlying the overexpression of glypican-3 in neuroblastoma warrant further investigations, especially the promising use of glypican-3 for diagnostic and therapeutic purposes.