Immunohistochemical Assessment of Differentiation and DNA Replication in Human Brain Tumors

The introduction of immunohistochemicar methods has had a profound impact both on the science and practice of neuropathology. In many ways it has changed our way of thinking about neuro-oncogenesis (Rubinstein 1987a), and in surgical pathology, it has led to a significantly higher level of diagnostic accuracy (Bonnin and Rubinstein 1984; Kleihues et al. 1987). However, the application of immunocytochemical markers has not profoundly affected our view on the current classification of brain tumors (Zulch 1979) although in a few cases it led to the abolishment of established entities (e.g., monstrocellular sarcoma) and the introduction of new diagnostic terms (e.g., the polymorphic xanthoastrocytoma). It should, however, be kept in mind that with respect to the histogenesis of neoplasms, the use of lineage-specific marker antigens may lead to erroneous interpretations. In contrast to their normal counterparts, neoplastic cells may undergo unpredictable changes in gene expression. This may result in the lack of a gene product typically present, or in the synthesis of a marker protein not usually expressed, in the cell of origin. Also, the panel of antibodies currently available offers no help in distinguishing normal from highly differentiated neoplastic cells. In this contribution we wish expand on two problems in which immunohistochemical markers have become increasingly useful, i.e. the assessment of cell kinetic parameters and analysis of the extent and direction of differentiation in embryonal CNS tumors.