Immunohistochemical expression of apoptosis regulating proteins and sex hormone receptors in meningiomas

Meningiomas are well known to be responsive to estrogen/progesterone stimulation, and their expression of estrogen/progesterone receptor (ER/PR) has been documented. On the other hand, there are several reports studying expression of apoptosis-regulating proteins (ARPs) and its significance in meningiomas. However, very limited published information exists on the exact relation among sex hormone receptor status, apoptosis, proliferation index (PI), and histological grade in meningiomas. A total of 57 cases of non-malignant meningiomas were selected, and histologically reviewed and graded (WHO grades 1, 2). All these cases were immunostained for ER, PR, Ki-67, and ARPs including bax, bcl-2, and bcl-xL. Sections were graded semiquantitatively for intensity and extent of immunostaining. PI was expressed as a percentage of Ki-67 positive tumor cells. Expression of bax, bcl-2, bcl-xL, ER, and PR was seen in 100, 35.1, 24.6, 10.4, and 87.2% of cases, respectively. Bax was expressed diffusely and strongly, while Bcl-2 tended to be expressed weakly and focally. Bcl-xL appeared to be expressed relatively strongly and diffusely in a small subset. There was significantly higher PI as well as expression of PR in grade 1 group than in grade 2 group. A weak negative correlation was observed between Bcl-2 and PR (r = -0.472, P < 0.0014). Given high-level expression of pro-apoptotic bax, which seems to be constitutionally expressed, in contrast to low-level expression of antiapoptotic bcl-2 and bcl-xL, other antiapoptotic proteins may involve the proliferation of meningiomas. A significant negative relation exists between PR and Bcl-2 in meningiomas, which might have some biological and clinical significance.