Alternative EWS‐FLI1 fusion gene and MIC2 expression in peripheral and central primitive neuroectodermal tumors

Abstract

Primitive neuroectodermal tumors (PNET) occur either in the central nervous system (CNS; central PNET, cPNET) or in the peripheral sites (peripheral PNET, pPNET). Recent molecular approaches have been defining a new concept of PNET, that is, the pPNET including Ewing's sarcoma (ES) which expresses MIC2 glycoprotein and shows the specific chimeric gene of EWS‐FLI1. The expression of MIC2 and the genetic rearrangement of EWS‐FLI1 are considered to be highly specific to the pPNET/ES. This study examined the expression of MIC2 and EWS‐FLI1 gene by means of immunohistochemistry and reverse transcriptase–polymerase chain reaction (RT‐PCR) on various small round cell tumors originating in the CNS or non‐CNS organs. All peripheral PNET tested expressed MIC2 and were positive for EWS‐FLI1 (11/11). In contrast, all cPNET and other blastic CNS tumors were negative for MIC2: medulloblastoma (0/3), cerebral PNET (0/2), spinal PNET (0/2), glioblastoma (0/2), retinoblastoma (0/3), and pineoblastoma (0/2). These MIC2‐negative tumors were also negative for the chimeric gene product of EWS‐FLI1. Interestingly, one PNET originating in the intracranial dura mater was positive for both MIC2 and EWS‐FLI1 fusion gene. The results indicate that cPNET lacks any genetic or protein markers, except for a meningeal PNET which falls into the same phenotypic spectrum of pPNET.