Expression of the c-erbB-2-encoded oncoprotein and progesterone receptor in human meningiomas

Abstract

The present study investigated the expression of c-erbB-2 in 59 meningiomas, including different histological subtypes and anaplastic variants, by immunocytochemistry and molecular biological techniques. Immunohistochemistry using the monoclonal antibody FWP-51 directed against c-erbB-2-encoded oncoprotein gp185 demonstrated variable degrees of immunoreactivity in all meningiomas. The intensity of immunostaining correlated with the degree of expression as assessed by Western analysis in 28 meningiomas using polyclonal antiserum 21N. There was no correlation between the degree of expression and histological variants. Immunoreactivity of all meningiomas was distinctly less intense, however, than that of the human breast cancer cell line SK-BR-3, and slightly lower than that of brain metastases of breast and ovarian carcinomas that served as positive controls for both methods. By Southern analysis all meningiomas showed a single copy of the c-erbB-2 gene. Non-neoplastic arachnoid cap cells also exhibited c-erbB-2 expression and the degree of immunoreactivity was comparable with the majority of meningiomas. These data argue against an overexpression of c-erbB-2 in meningiomas, but rather indicate a cell-type-specific constitutive expression of the c-erbB-2 gene product in meningiomas and their putative progenitor cells. Since a subgroup of meningiomas is known to express progesterone receptors (PR), gp185 immunoreactivity was compared to the hormone receptor status using monoclonal antibody KD68. Fifty-six percent meningiomas showed PR immunoreactivity, but there was no statistically significant correlation with the degree of gp185 expression.

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

“…In the present study, Her-2/neu expression was also significantly higher in meningothelial meningiomas, suggesting that Her-2/ neu expression may be associated with differentiation. No relationship has been described between Her-2/ neu overexpression and proliferative activity in previous studies, [9][10][11][12][13][14][15][16] and our results support this finding.…”

“…[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.…”

“…[15,16] In contrast, Schlegel et al [14] and Potti et al [10,11] detected Her-2/ neu in non-neoplastic arachnoid cap cells. In the current study, we also observed Her-2/neu immunoreactivity at low levels in non-neoplastic meningeal tissues.…”

“…[8,9] However, the significance of Her-2/neu expression in meningiomas is currently unknown. [10][11][12][13][14][15][16] In the present study, we analyzed the immunohistochemical expression of the PR, ER, and Her-2/neu in WHO grade I meningiomas. In addition, we related the expression profiles of these factors to clinicopathological parameters such as age, gender, tumour size, brain and dura invasion, histological subtype, and proliferative index.…”

ErbB-2 Activates Stat3α in a Src- and JAK2-dependent Manner

“…Although no ligand that specifically binds to ErbB-2 has been identified, the ErbB-2 receptor is reported to form homodimers or heterodimers with other ErbB family members and may contribute to changes in downstream gene expression profiles (16). Overexpression or abnormal activation of ErbB-2 is found in tumors such as brain (17), head, and neck (18), breast cancer (19), non-small-cell lung cancer (20), bladder cancer (21), and melanoma (22). Furthermore, ErbB-2 expression is also correlated with poor prognosis due to the resistance to chemotherapy (23) and increased metastasis (24,25).…”