GLIAL DIFFERENTIATION PREDICTS POOR CLINICAL OUTCOME IN PRIMITIVE NEUROECTODERMAL BRAIN-TUMORS

Primitive neuroectodermal tumors (PNETs) of the central nervous system , including medulloblastomas (PNET/MB), are the most common malignant brain tumor of childhood. These tumors often express proteins characte ristic of glial differentiation (glial fibrillary acidic protein, GFAP ), neuronal differentiation (neurofilament proteins, NFPs), and/or pho toreceptor differentiation (retinal-S antigen). To identify biological factors of prognostic significance in PNETs, the expression of glial, neuronal, or photoreceptor antigens was evaluated in the tumor specim ens of 86 patients with PNETs by immunohistochemistry after microwave antigen enhancement. Patterns of differentiation were then compared wi th patient relapse-free survival. Multivariate analysis of PNET immuno histochemistry and clinical variables indicated GFAP expression confer red a 6.7-fold greater risk of relapse than tumors that did not expres s GFAP or NFPs. Increased risk of relapse was directly related to the amount of GFAP expression. Tumors exhibiting dumps or sheets of GFAP-s taining cells were associated with a 3.0-fold increased risk of relaps e compared with tumors that did not express GFAP, irrespective of immu nohistochemical evidence of other differentiation, while scattered GFA P staining was not associated with increased risk of relapse. These fi ndings indicate that expression of GFAP in PNETs has prognostic power comparable with the most significant clinical factors currently used t o predict clinical outcome.