Cells with intense EGFR staining and a high nuclear to cytoplasmic ratio are specific for infiltrative glioma: a useful marker in neuropathological practice

摘要: Infiltrative gliomas (IG), including astrocytomas, oligodendrogliomas, and glioblastomas, are the most common primary brain tumors in humans.1 IG display a poor prognosis, especially which represent aggressive subtype.1 The of this group characterized by pattern infiltrative growth into surrounding normal brain,2 making complete surgical excision very difficult. Recurrence or progression after surgery almost always occurs despite adjuvant treatment with radiotherapy and/or chemotherapy.1 Morphological patterns often heterogeneous, diagnosis may be challenging for pathologists.2 Glial tumor cells also difficult to distinguish from reactive on basis morphology alone. Reactive astrocytes become large even pleomorphic nuclei resembling neoplastic cells.3 differential between gliosis can thus difficult, small biopsy samples.4 differentiate benign curable noninfiltrative glial tumors, pilocytic gangliogliomas, dysembryoplastic neuroepithelial tumors,1,2 demyelinating disease.5 It is therefore important pathologists develop histological markers identify infiltrating glioma cells. To date, no ideal marker has been identified purpose. In practice, useful MIB1/Ki676,7 p53,8,9 but these lack sensitivity specificity.10 More recently, mutated R132H form isocitrate dehydrogenase 1 (IDH1), specifically detected immunohistochemistry,11,12 shown good grade II III secondary glioblastomas.13–15 However IDH1 (R132H) rare glioblastomas16 not subtype, represents IG. A specific cells, characteristic regardless would value. Recently, we showed that EGFR immunolabelling discriminate low-grade gliosis.17 criterion was strong immunostaining high nuclear cytoplasmic ratio. overexpression frequent gliomas. 40% gene amplification associated expression EGFRvIII, constitutively activated variant.18 Conversely, gliomas,18–21 although protein frequency ranging 11.5% 100% cases literature.19,20,22–24 mechanism remains unknown. Several ligands, EGF TGFα, activate EGFR. activation involved several processes, cell survival, differentiation, proliferation, migration.25 Because influence migration during development central nervous system26–28 gliomas,29–31 postulated could migrating aim present study assess whether elevated ratio, as previously observed glioma,17 valuable any subtype lesions. We sought further characterize strongly EGFR-positive