ErbB receptors in human meningiomas
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Background: Meningiomas are the most common intracranial tumors in adults. They originate in the meninges, can grow to substantial size, and are in most cases benign. Recurrence; however, frequently occurs regardless of malignancy grade, and at present no molecular biomarkers are established for these tumors. Such markers could assist in the diagnostic process and in evaluating prognosis. In that regard, the ErbB receptor family is interesting. This is a group of four receptor tyrosine kinases (RTKs) that are of prognostic and therapeutic significance in several malignancies. These receptors have previously been examined in human meningiomas, but the results are somewhat ambiguous. Methods: In this thesis, the expression levels of EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 were assessed by means of immunohistochemistry in 186 operated intracranial meningiomas. The expression levels were tested for association with histological and clinical data. Also, the amplification status of HER2 was assessed with fluorescence in situ hybridization. Results: All ErbB-receptors are highly expressed in human meningiomas, but there are substantial differences in expression between the receptor domains. Non-neoplastic meningeal tissues were negative. Expression levels of EGFR extracellular domain, of phosphorylated HER2, and of HER4 were negatively associated with survival in univariable analyses. There was no amplification of the HER2 gene. Conclusion: The ErbB receptors are overexpressed in human meningiomas compared with normal meninges and may accordingly be of diagnostic value. Expression of the extracellular domain of EGFR, of phosphorylated HER2, and of HER4 may be of prognostic value in human meningiomas and should be investigated further.