Immunohistochemical evaluation of erbB-2 and p53 protein expression in benign and atypical human meningiomas

Abstract

Meningiomas arise from the arachnoidal cells surrounding the brain and are one of the most common tumors of the central nervous system. These tumors are known to be hormonally modulated and may occur in association with breast carcinoma. Overexpression of the erbB-2 oncogene product and mutation of the tumor suppressor p53 gene are considered causal 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 assigned a relative value of 0 to 5+, where 5+ denoted confluent immunoreactivity, 4+ to 1+ denoted varying degrees of focal positivity, and 0 denoted no evidence of staining. Levels of p53 and erbB-2 immunohistochemical 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 < 0.0001, Mann-Whitney U test). The inverse relationship between levels of erbB-2 and p53 immunoreactivity was found to be statistically significant (P < 0.0001, ANOVA). Expression of the erbB-2 protein was not associated with gene amplification or the presence of activating mutation in the transmembrane region of the protein. These findings may improve our understanding of the molecular events that occur in the neoplastic transformation of meningothelial cells. The patterns of erB-2 and p53 immunoreactivity may prove to be useful markers with which to identify potentially more malignant meningiomas.

Her-2/neu, Estrogen And Progesterone Receptor Expression In Who Grade I Meningiomas

“…[8] Her-2/neu is a well-known prognostic factor in various tumurs such as breast carcinoma, although the significance of Her-2/neu expression in meningiomas is unclear. [9][10][11][12][13][14][15][16][17] In our study, Her-2/neu overexpression was detected in 22.6% of the cases, which is within the range of 2.5 to 67.3% reported for Her-2/neu overexpression in meningiomas. [9][10][11][12][13][14][15][16][17] In a study by Loussouarn et al, [12] Her-2/neu overexpression was more frequent in meningiomas displaying epithelial differentiation, such as meningothelial and secretory types.…”

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

“…HER2/neu overexpression has been reported in an overwhelming majority of meningiomas despite their well-differentiated state, low-grade growth characteristics and very low metastatic potential [246][247][248][249][250]. By contrast, HER2/neu expression or overexpression has been reported as nonexistent, as with the normal embryologic expression pattern, and in some reports in up to 50% of gliomas across the range from low-grade astrocytomas to glioblastoma multiforme [247,[251][252][253][254][255][256][257][258][259][260][261] and a few activating mutations have been documented [262].…”

Original article Poly(ADP-ribose) polymerase-1 (PARP1) and p53 labelling index correlates with tumour grade in meningiomas

“…The role of p53 has already been examined in the meningiomas: some of the examinations ended with negative or equivocal findings [43,[48][49][50], but some of them showed a significant correlation between the p53 status and the grade or recurrence of the tumour [4,7,8,19,20,28,37,41,44,46,57]. It is also described that p53 immunopositive cells are more frequent in the perinecrotic areas of post-embolised cases than in preserved parts of the tumour [39].…”