TY - JOUR
T1 - Hu immunolabeling as a marker of neural and neuroendocrine differentiation in normal and neoplastic human tissues
T2 - Assessment using a recombinant anti-Hu Fab fragment
AU - Gultekin, S. Humayun
AU - Rosai, Juan
AU - Demopoulos, Alexis
AU - Graus, Yvo F.
AU - Posner, Jerome B.
AU - Dalmau, Josep
AU - Rosenblum, Marc K.
PY - 2000/4
Y1 - 2000/4
N2 - The recombinant antibody fragment Fab GLN 495 recognizes an epitope shared by members of the neuron-associated Hu protein family (including HuC, HuD, and HelN1). 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 neuronal phenotype or neuronogenic differentiating capacity. Using this Fab fragment, 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, paraganglial chief cells, isolated adenohypophyseal cells, and spermatogonia were the only nonneuronal normal tissue elements to bind Fab GLN 495. In addition to labeling all 10 small cell carcinomas studied (six of which were extrapulmonary in origin), this recombinant anti-Hu Fab proved immunoreactive with neuroblastomas (four/four), esthesioneuroblastomas (one/one), typical (three/four) and atypical (one/four) pulmonary carcinoids, pancreatic islet cell 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). Nonneural/neuroendocrine tumor labeling was restricted to the neuronal and immature neuroepithelial components of teratomas, to extraskeletal myxoid chondrosarcomas (three/four) and to small subsets of cells within examples of renal rhabdoid tumor (one/four), desmoplastic small cell tumor (one/four), alveolar rhabdomyosarcoma (two/four), Ewing sarcoma/PNET (two/nine), and Wilms tumor (one/four). Immunoreactivity was principally nuclear, with variable cytoplasmic labeling. Our findings support the largely restricted expression of Hu by neural/neuroendocrine neoplasms, suggest a potential role for Fab GLN 495 in the identification of small cell carcinomas irrespective of primary site, and support a recent proposal that at least some extraskeletal myxoid 'chondrosarcomas' actually represent neuroendocrine tumors of soft parts.
AB - The recombinant antibody fragment Fab GLN 495 recognizes an epitope shared by members of the neuron-associated Hu protein family (including HuC, HuD, and HelN1). 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 neuronal phenotype or neuronogenic differentiating capacity. Using this Fab fragment, 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, paraganglial chief cells, isolated adenohypophyseal cells, and spermatogonia were the only nonneuronal normal tissue elements to bind Fab GLN 495. In addition to labeling all 10 small cell carcinomas studied (six of which were extrapulmonary in origin), this recombinant anti-Hu Fab proved immunoreactive with neuroblastomas (four/four), esthesioneuroblastomas (one/one), typical (three/four) and atypical (one/four) pulmonary carcinoids, pancreatic islet cell 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). Nonneural/neuroendocrine tumor labeling was restricted to the neuronal and immature neuroepithelial components of teratomas, to extraskeletal myxoid chondrosarcomas (three/four) and to small subsets of cells within examples of renal rhabdoid tumor (one/four), desmoplastic small cell tumor (one/four), alveolar rhabdomyosarcoma (two/four), Ewing sarcoma/PNET (two/nine), and Wilms tumor (one/four). Immunoreactivity was principally nuclear, with variable cytoplasmic labeling. Our findings support the largely restricted expression of Hu by neural/neuroendocrine neoplasms, suggest a potential role for Fab GLN 495 in the identification of small cell carcinomas irrespective of primary site, and support a recent proposal that at least some extraskeletal myxoid 'chondrosarcomas' actually represent neuroendocrine tumors of soft parts.
KW - Anti-Hu
KW - Antineuronal autoantibodies
KW - Human tumors
KW - Neuroendocrine tumors
KW - Paraneoplastic syndromes
KW - Recombinant antibodies
KW - Small cell carcinoma
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U2 - 10.1177/106689690000800205
DO - 10.1177/106689690000800205
M3 - Article
AN - SCOPUS:0034046989
SN - 1066-8969
VL - 8
SP - 109
EP - 117
JO - International Journal of Surgical Pathology
JF - International Journal of Surgical Pathology
IS - 2
ER -