RECEPTOR TYROSINE KINASE EXPRESSION IN ASTROCYTIC LESIONS - SIMILAR FEATURES IN GLIOSIS AND GLIOMA

THE PURPOSE OF this study was to determine if the expression of recept or tyrosine kinases would distinguish astrocytosis from astrocytoma. B ecause the expression of this family of receptor proteins is greater i n higher-grade tumors, a graded series of both reactive and neoplastic astrocytic lesions in humans was evaluated. The reactive processes in cluded both mild gliosis and severe (intense) gliosis. The two immunoc ytochemically detected membrane receptor proteins, p145 and p185, are those encoded by the kit and neu genes, respectively. Semi-quantitativ e assessments were made independently for the frequency and intensity of astrocytic immunostaining together with corollary immunocytochemica l staining to detect glial fibrillary acidic protein. It was found tha t both mild gliosis and low-grade astrocytomas only minimally express these receptors. In contrast, severe gliosis and high-grade neoplasms consistently express these receptors at much higher levels. In both as trocytosis and astrocytomas, a cell with abundant perikaryal cytoplasm is most likely to be immunoreactive, often with dense reaction produc t concentrated at the periphery of the somal cytoplasm. The extent and pattern of immunoreactivity in high-grade astrocytomas preclude the i nterpretation that all immunoreactive cells were merely reactive astro cytes. We conclude that the expression of these receptors per se does not differentiate astrocytic neoplasia from reactive astrocytosis. Sec ond, we conclude that immunocytochemically detectable levels of neu or kit receptor expression is not constitutive in normal astrocytes and in some stages of astrocytic neoplasia. On the basis of these findings , we speculate that some neoplastic astrocytes maintain and manifest t he capacity to respond to transitory exogenous stimuli, as do reactive astrocytes. This reaction could include the elaboration of receptor t yrosine kinases. Alternatively, even if the function of these receptor s in gliosis differs from that in gliomas, the common expression could still reflect an ''active'' state shared by astrocytes in these two p rocesses.