PROTEINS OF THE INTERMEDIATE FILAMENT CYTOSKELETON AS MARKERS FOR ASTROCYTES AND HUMAN ASTROCYTOMAS

There is a pressing need for a more accurate system of classifying hum an astrocytomas, one that is based on morphologic characteristics and that could also make use of distinctive biochemical markers. However, little is known about the phenotypic characteristics of astrocytomas. Recent studies have shown that the expression of proteins comprising t he intermediate filament (IF) cytoskeleton of astrocytic cells is deve lopmentally regulated. It is our hypothesis that this changing protein profile can be used as the basis of a system for clearly and objectiv ely classifying astrocytomas. A spectrum of human astrocytomas has bee n examined by immunofluorescence microscopy employing antibodies to se veral IF structural subunit proteins (GFAP, vimentin, and keratins) an d an IF-associated protein, IFAP-300kDa. These proteins occupy unique temporal niches in the cytogenesis of the astrocytic cells: keratins i n cells of the neuroectoderm; vimentin and IFAP300-kDa in radial glia and immature glia; GFAP in mature astrocytes; and vimentin in some mat ure astrocytes. In agreement with previous reports, our immunofluoresc ence studies have revealed both GFAP and vimentin in all astrocytoma s pecimens. Two new observations, however, are of particular interest: I FAP-300kDa is detectable in all astrocytic tumors, and the proportion of keratin-containing cells present in the astrocytomas is in direct r elationship to the degree of the malignancy. Because IFAP-300kDa is no t present in either normal mature or reactive astrocytes, this protein appears to represent a specific marker of transformed (malignant) ast rocytes. If it is presumed that higher malignancy grades represent the most dedifferentiated cellular state of the astrocytes, the presence of keratin-containing cells is not totally unexpected, given the ectod ermal (epithelial) origin of the CNS. Specific developmentally regulat ed proteins of the IF cytoskeleton thus appear to hold great potential as diagnostic markers of astrocytomas and as tools for investigating the biology of these tumors.