Hu immunolabeling as a marker of neural and neuroendocrine differentiationin normal and neoplastic human tissues: Assessment using a recombinant anti-Hu Fab fragment

The recombinant antibody fragment Fab GLN 495 recognizes an epitope shared by members of the neuron-associated Hu protein family (including HuC, HuD, and Hel-N1). This novel reagent labels the nuclei of neurons throughout the peripheral and central neuraxes and has been shown to recognize pulmonary small cell carcinomas and central nervous system (CNS) tumors of mature neu ronal phenotype or neuronogenic differentiating capacity. Using this Fab fr agment, we have undertaken a systematic survey of normal human tissues and an assessment of 554 non-CNS tumor samples for immunohistochemical evidence of Hu expression. Adrenomedullary cells, pancreatic islet cells, paragangl ial chief cells, isolated adenohypophyseal cells, and spermatogonia were th e only nonneuronal normal tissue elements to bind Fab GLN 495. In addition to labeling all 10 small cell carcinomas studied (six of which were extrapu lmonary in origin), this recombinant anti-Hu Fab proved immunoreactive with neuroblastomas (four/four), esthesioneuroblastomas (one/one), typical (thr ee/four) and atypical (one/four) pulmonary carcinoids, pancreatic islet cel l tumors (two/six), large-cell neuroendocrine carcinoma of lung (one/four), Merkel cell tumors (two/three), medullary carcinomas of the thyroid (four/ six), pheochromocytomas (two/four) and paragangliomas (four/four). Nonneura l/neuroendocrine tumor labeling was restricted to the neuronal and immature neuroepithelial components of teratomas, to extraskeletal myxoid chondrosa rcomas (three/four) and to small subsets of cells within examples of renal rhabdoid tumor (one/four), desmoplastic small cell tumor (one/four), alveol ar rhabdomyosarcoma (two/four), Ewing sarcoma/PNET (two/nine), and Wilms tu mor (one/four). Immunoreactivity was principally nuclear, with variable cyt oplasmic labeling. Our findings support the largely restricted expression o f Hu by neural/neuroendocrine neoplasms, suggest a potential role for Fab G LN 495 in the identification of small cell carcinomas irrespective of prima ry site, and support a recent proposal that at least some extraskeletal myx oid "chondrosarcomas" actually represent neuroendocrine tumors of soft part s.