Immunohistochemical demonstration of phosphorylated and nonphosphorylated forms of human neurofilament subunits in human pulmonary carcinoids.
Using immunohistochemical tests and monoclonal antibodies specific for phosphorylated isoforms of the high-molecular-weight human neurofilament subunit (NF-H) or for nonphosphorylated isoforms of NF-H and the middle-molecular-weight NF protein, we detected phosphorylated and nonphosphorylated NF protein isoforms in typical central bronchial carcinoids but not in atypical or peripheral carcinoids or in small cell undifferentiated carcinomas of the lung. Immunoreactive NF protein was seen largely in juxtanuclear globular aggregates which may correspond to cytoplasmic whorls of intermediate filaments observed in one of the tumors by electron microscopy. A monoclonal antibody to low-molecular-weight keratin polypeptides immunostained similar aggregates in central bronchial carcinoids. The precursor cells of human pulmonary carcinoids and the mechanisms leading to abnormal aggregates of NF and keratin immunoreactivity are unknown. However, the preponderance of phosphorylated NF epitopes as compared with nonphosphorylated forms in the cell bodies of carcinoid tumor cells implicates abnormal phosphorylation states in the formation of these intermediate filament aggregates. Our data do not confirm that antibodies to NF-H are helpful for the diagnosis of undifferentiated lung carcinomas, but they can distinguish subsets of bronchial carcinoids with different biological behaviors and growth potentials.
Christen
B
B
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Trojanowski
J Q
JQ
Pietra
G G
GG
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D001984:Bronchial Neoplasms / Q000648:ultrastructure*; D003528:Carcinoma, Adenoid Cystic / Q000648:ultrastructure*; D018288:Carcinoma, Small Cell / Q000648:ultrastructure*; D003599:Cytoskeleton / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007382:Intermediate Filaments / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure*; D008175:Lung Neoplasms / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010766:Phosphorylation
D000911:Antibodies, Monoclonal