Cytokeratin AE1/AE3 mimicry in glioblastoma

Abstract

INTRODUCTION : The diagnosis and treatment of intracranial tumors requires a multidisciplinary approach. A key moment in this process is the pathological verification of the tumor type. This process, although aided by immunohistochemistry (IHC), can often be difficult and misleading. MATERIALS AND METHODS : Ten histologically confirmed cases of glioblastoma multiforme (GBM) were reviewed for their IHC reaction with the anti-glial fibrillary acidic protein (GFAP) glial marker and the CK AE1/AE3 antibody cocktail, whose main use in neuropathology is to either prove or rule out metastatic cancer of epithelial origin, the primary location of which may not be known or even suspected. RESULTS : All ten pathologically verified cases of GBM were diagnostically positive for GFAP, with eight of them also revealing CK AE1/AE3 expression with variable intensity. Out of the CK AE1/AE3 positive cases, five (50% in total) gave a low to intermediate non-diagnostic positive reaction, while the other three cases (30% in total) gave a strong positive reaction with possible diagnostic value. Cells, across all GBM cases, that tested positive for CK AE1/AE3, regardless of the strength of the reaction, were also positive for GFAP on neighboring IHC serial slides. CONCLUSION : The presented results reveal CK AE1/AE3 expression in a great portion of GBM cases, which may be caused by three-dimensional mimicry between the CK AE1/AE3 and GFAP target molecules. This therefore necessitates the need for a careful interpretation of the results. CK AE1/AE3, however, remains a useful tool in neuropathology, regardless of the possibility of false positivity in GBM cells.