DETECTION OF TUMOR NECROSIS FACTOR-EX PROTEIN AND MESSENGER-RNA IN HUMAN GLIAL BRAIN-TUMORS - COMPARISON OF IMMUNOHISTOCHEMISTRY WITH IN-SITU HYBRIDIZATION USING MOLECULAR PROBES

Tumor necrosis factor-alpha (TNF alpha) protein and messenger (m)RNA d istribution was studied in biopsy samples of glial brain tumors, using immunohistochemistry and in situ hybridization with molecular probes, to investigate the role of this cytokine in tumor proliferation and i mmunological host defense. Focal expression of TNF alpha was detected in four of four glioblastomas, one of two anaplastic astrocytomas, and four of five low-grade astrocytomas, regardless of their subtype or g rade of malignancy, but in none of the normal peritumoral brain tissue s used as controls. The TNF alpha protein and mRNA were present in rea ctive astrocytes and protoplasmic tumor cells, confined to areas of le ukocyte or T-lymphocyte infiltration, and less pronounced in tumor cel ls at the edge of necrosis. Additionally, TNF alpha reactivity was fou nd in infiltrating macrophages and perivascular microglia. Immunohisto chemistry and in situ hybridization for TNF alpha showed comparable re action patterns and numbers of TNF alpha-positive cells, even though t he sensitivity of in situ hybridization was significantly higher. Quan titative evaluation of TNF alpha protein, TNF alpha mRNA, and leukocyt e infiltration revealed a significant positive correlation between the TNF alpha-positive reactive astrocytes and the number of lymphocytes present in corresponding areas. Together, these data lead to the concl usion that TNF alpha in reactive astrocytes and monocytic cells within tumor areas of high leukocyte infiltration and in tumor cells at the border of necrosis may represent one defense pathway of the immune sys tem against tumor proliferation.