IMMUNOHISTOCHEMICAL EVALUATION OF ERBB-2 AND P53 PROTEIN EXPRESSION IN BENIGN AND ATYPICAL HUMAN MENINGIOMAS

Meningiomas arise from the arachnoidal cells surrounding the brain and are one of the most common tumors of the central nervous system. Thes e tumors are known to be hormonally modulated and may occur in associa tion with breast carcinoma. Overexpression of the erbB-2 oncogene prod uct and mutation of the tumor suppressor p53 gene are considered causa l driving forces in the pathogenesis of adenocarcinomas of the breast. To determine whether abnormal expression of these genes also plays a role in the pathogenesis of meningiomas, we analyzed the expression of the erbB-2 and p53 proteins in 17 atypical and 35 typical meningioma tissue specimens by immunohistochemistry. The staining intensity was a ssigned a relative value of 0 to 5+, where 5+ denoted confluent immuno reactivity, 4+ to 1+ denoted varying degrees of focal positivity, and 0 denoted no evidence of staining. Levels of p53 and erbB-2 immunohist ochemical staining were then correlated with tumor histology. For p53 immunoreactivity, typical meningiomas had a median staining score of 1 .0, compared to 4.0 for atypical meningiomas (P<0.0001, Mann-Whitney U test). For erbB-2 immunoreactivity, typical meningiomas had a median staining score of 5.0 compared to 1.0 for atypical meningiomas (P<0.00 01, Mann-Whitney U test). The inverse relationship between levels of e rbB-2 and p53 immunoreactivity was found to be statistically significa nt (P<0.0001, ANOVA). Expression of the erbB-2 protein was not associa ted with gene amplification or the presence of activating mutations in the transmembrane region of the protein. These findings may improve o ur understanding of the molecular events that occur in the neoplastic transformation of meningothelial cells. The patterns of erbB-2 and p53 immunoreactivity may prove to be useful markers with which to identif y potentially more malignant meningiomas.