INTERMEDIATE FILAMENT PROTEINS AS TUMOR MARKERS

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Intermediate filaments (IF) are the 10-12 nm in diameter cytoskeletal structures of nucleated mammalian cells. Five different classes are distinguished, and three are present in cells of the central (CNS) and peripheral (PNS) nervous system: neurofilaments (IF of neurons), glial filaments (IF of CNS glia), and vimentin (IF of CNS and PNS glia as well as of mesenchymal and other cells). The two other classes of IF are desmin (IF of muscle cells) and keratin (IF of epithelial cells). Thus, except for vimentin, IF proteins are cell specific and can be considered cell type-specific markers in oncological pathology. Antisera (AS) against different IF classes have been used with some success in diagnostic pathology. However, the use of anti-IF AS has resulted in conflicting reports on the cellular distribution of certain IF classes. Recent studies, using anti-IF monoclonal antibodies (MAs), suggest that this may be due to the fact that the different IF classes have both unique and shared epitopes. This potential obstacle to the use of anti-IF antibodies in diagnostic pathology can be overcome through the use of MAs specific for individual IF classes. Studies will carefully evaluate the hypothesis that anti-IF class-specific MAs are useful reagents for the evaluation of human CNS and PNS tumors (including tumors of the diffuse neuroendocrine system or apudomas). IF proteins of each class will be purified and used to produce class-specific MAs, which will be characterized by immunochemical and immunohistochemical methods. The distribution of each IF class will be determined using these MAs by immunohistochemistry in normal and neoplastic CNS and PNS tissues. Pending these results, spinal fluid cytology specimens will also be examined. In addition, electron microscopy and immunochemical methods will be used to further characterize the IF of selected tumors. These studies will lead to improvements in tumor diagnosis, patient care, and the understanding of tumor biology. (4)