HER3 and HER4 are highly expressed in human meningiomas

Abstract HER3 and HER4 are tyrosine kinase receptors of the ErbB family that have been detected in several cancers but lack substantial investigation in human meningiomas. In this study, HER3 and -4 expression levels were evaluated as potential biomarkers by immunohistochemistry and explored for association to clinical features in a large series of human meningiomas. 186 primary intracranial meningiomas from adult patients were investigated with antibodies against HER3 and -4 intracellular domains. Tumors were scored with a staining index (SI) based on cytoplasmic/membranous staining intensity and on the percentage of positive cells. SIs were tested for associations with WHO malignancy grade, tumor subtype, localization, and prognosis. HER3 and HER4 were highly expressed in most tumors. Both cytoplasmic and membranous immunoreactivity occurred, and for HER4 nuclear immunoreactivity was observed as well. Non-neoplastic meningeal tissue was not immunoreactive. HER3 and -4 immunoreactivity was not associated with WHO malignancy grade, nor with recurrence or survival in adjusted analyses. Meningiomas of all grades were shown to widely express both HER3 and HER4 receptors. This feature may have diagnostic value since non-neoplastic meninges were not immunoreactive. There was no prognostic significance in adjusted survival analyses.