ANTI-HU IMMUNOLABELING AS AN INDEX OF NEURONAL DIFFERENTIATION IN HUMAN BRAIN-TUMORS - A STUDY OF 112 CENTRAL NEUROEPITHELIAL NEOPLASMS

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 neur on restricted and that appear to be integral to neuronal differentiati on and maintenance, selectively label the nuclei (and, less strongly, the cytoplasm) of neurons throughout the human neuraxis. Small cell ca rcinomas of the lung and many neuroblastomas are also labeled. We scre ened 112 tumors of central neuroepithelial lineage for immunohistochem ical evidence of Hu expression with anti-Hu immunoglobulin G that was purified from patient sera and with a recombinant Fab fragment (Fab GL N 495) selected from a patient-derived combinatorial antibody phage di splay library using a recombinant Hu protein (HuD). Both antibodies un iformly labeled, in addition to native neurons, the nuclei of central neurocytomas (6 of 6) and the neuronal components of ''classic'' (12 o f 12) and desmoplastic infantile (2 of 2) gangliogliomas. Of 33 embryo nal tumors, 29 were anti-Hu reactive, including 87% of medulloblastoma s (26 of 30). Glial neoplasms (n = 59) were anti-Hu negative save for one ''oligodendroglioma'' (of 17 oligodendroglial/oligoastrocytic tumo rs) that may have been an extraventricular neurocytoma. Anti-Hu immuno globulin S/Fab GLN 495 identifies neoplasms of differentiated neuronal type and embryonal tumors with neuronogenic potential.