Region Specific Differences of Claudin-5 Expression in Pediatric Intracranial Ependymomas: Potential Prognostic Role in Supratentorial Cases

Abstract

Ependymomas are common pediatric brain tumors that originate from the ependyma and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict outcome. In a retrospective study, we analyzed 54 intracranial pediatric ependymomas and found a significantly higher overall survival in supratentorial cases when compared to infratentorial tumors. Next we performed region-specific immunohistochemical analysis of the ependyma in neonatal and adult ependyma from the central canal of spinal cord to the choroid plexus of lateral ventricles for components of cell-cell junctions including cadherins, claudins and occludin. We found robust claudin-5 expression in the choroid plexus epithelia but not in other compartments of the ependyma. Ultrastructural studies demonstrated distinct regional differences in cell-cell junction organization. Surprisingly, we found that 9 out of 20 supratentorial but not infratentorial ependymomas expressed high levels of the brain endothelial tight junction component claudin-5 in tumor cells. Importantly, we observed an increased overall survival in claudin-5 expressing supratentorial ependymoma. Our data indicates that claudin-5 expressing ependymomas may follow a distinct course of disease. The assessment of claudin-5 expression in ependymoma has the potential to become a useful prognostic marker in this pediatric malignancy.

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…Claudin-5, the prototypical BBB claudin, distributes at the junctions in large penetrating stromal vessels in rat and mouse and possibly in some smaller vessels [74,82,146]. Its expression in the choroidal epithelium was not detected in rat and mouse, but was recently described in human neonates [164]. Claudin-11 was immunodetected at epithelial junctions in mouse choroid plexus [166].…”

Squash cytology findings of subependymomas: A report of three cases and differential diagnosis

“…Claudin‐5 is a protein of tight junction membranes reported to be expressed by endothelial cells of the brain and ependymoma tumor cells . Immunohistochemical analysis showed that claudin‐5 (Abcam plc, Cambridge, UK) was expressed in the endothelial cells of all three subependymomas and in an ependymoma.…”

“…Microcysts containing mucoid material were frequently observed ( Figure 3A Claudin-5 is a protein of tight junction membranes reported to be expressed by endothelial cells of the brain and ependymoma tumor cells. 8,9 Immunohistochemical analysis showed that claudin-5 (Abcam plc, Cambridge, UK) was expressed in the endothelial cells of all three subependymomas and in an ependymoma. The subependymomas and the ependymoma sample showed focal intracytoplasmic dot-like and cytoplasmic membrane expression of claudin-5 ( Figure 3C,D), with the ependymoma sample also showing linearly strong positive staining for claudin-5 at the lumina of the ependymal rosettes ( Figure 3D).…”