title: Anti-Hu immunolabeling as an index of neuronal differentiation in human brain tumors: a study of 112 central neuroepithelial neoplasms.
abstract: Anti-Hu is a polyclonal immunoglobulin G associated with a syndrome of paraneoplastic sensory neuropathy/encephalomyelitis that principally afflicts patients with small cell lung carcinoma. Anti-Hu antibodies, which identify a family of RNA-binding proteins that are normally neuron restricted and that appear to be integral to neuronal differentiation and maintenance, selectively label the nuclei (and, less strongly, the cytoplasm) of neurons throughout the human neuraxis. Small cell carcinomas of the lung and many neuroblastomas are also labeled. We screened 112 tumors of central neuroepithelial lineage for immunohistochemical evidence of Hu expression with anti-Hu immunoglobulin G that was purified from patient sera and with a recombinant Fab fragment (Fab GLN 495) selected from a patient-derived combinatorial antibody phage display library using a recombinant Hu protein (HuD). Both antibodies uniformly labeled, in addition to native neurons, the nuclei of central neurocytomas (6 of 6) and the neuronal components of "classic" (12 of 12) and desmoplastic infantile (2 of 2) gangliogliomas. Of 33 embryonal tumors, 29 were anti-Hu reactive, including 87% of medulloblastomas (26 of 30). Glial neoplasms (n = 59) were anti-Hu negative save for one "oligodendroglioma" (of 17 oligodendroglial/oligoastrocytic tumors) that may have been an extraventricular neurocytoma. Anti-Hu immunoglobulin G/Fab GLN 495 identifies neoplasms of differentiated neuronal type and embryonal tumors with neuronogenic potential.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Gultekin
authors.forename: J
authors.initials: J
authors.lastname: Dalmau
authors.forename: Y
authors.initials: Y
authors.lastname: Graus
authors.forename: J B
authors.initials: JB
authors.lastname: Posner
authors.forename: M K
authors.initials: MK
authors.lastname: Rosenblum
mesh_terms: D000912:Antibodies, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; D006801:Humans; D018302:Neoplasms, Neuroepithelial / Q000276:immunology / Q000473:pathology*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000276:immunology / Q000473:pathology*; D016601:RNA-Binding Proteins / Q000276:immunology*
chemical_list: D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498010:ELAVL4 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins