Significances Of The Expression Of MDM2 And Bcl-2 Association With Androgen Receptor Expression In Meningiomas

Objective: Meningiomas have long been suspected to have a hormonal link based on their epidemiological and biological characters. The expression of the progesterone receptor has been used as a target for therapeutic intervention in meningioma patients, but with mixed results, possibly due to a lack of a clear understanding of the biological characters of meningiomas. At present researches are focused on the correlation between apoptosis and sex hormone receptors as well as the choice of the target for hormonal therapy. By this research we aim mostly at to observe the relation between the apoptosis-related proteins mdm2, bcl-2 and androgen receptor, which may be a new therapeutic target for meningiomas. By the way we have partly investigate the epidemiological status of the meningioma patients locally, and have posted the relation between pathologic types and above-mentioned three factors in meningiomas.Methods: Data on 394 pathologically verified meningiomas were obtained from pathologic department, HuanXi hospital. Computer gained 60 random samples. We finally obtain 60 paraffin-embedded meningioma specimens. Then sections from these samples were subjected to immunohistochemical analysis with antibodies directed against mdm2,bcl-2 and the androgen receptor by LSAB method. Because androgen receptor expression was mostly nuclear whereas mdm2 and bcl-2 were mostly cytoplasmic, we determine only the nature positive or negative for androgen receptor still the partial quantity for mdm2 and bcl-2. In this research we adopt blind method not only the results estimation but also the statistical analysis for mdm2 and bcl-2 expression.Results: (1) Meningiomas occur at the age of 30—69 mainly and centralize at the age of 50—59 (119/394) . The ratio between male and female is 1/2.48 in all cases. (2) In those cases age no more than 30 or more than 69 the ratio between male and female patients is respectively 1.4/1 or 1.6/1 against the ratio in all cases. (3) According to WHO pathologic classification I, II and III the proportion of those meningiomas in the cohort is 67%, 26% and 7% respectively. (4) The proportion of male meningiom patients having a ascending trend going with pathologic tumor score is 32.7%, 42.3% and 46% respectively in grade I, II and III. (5) Mdm2 and bcl-2 expression were mostly cytoplasmic and androgen receptor expression was mostly nuclear and there was no statistically significant correlation between them. (6) The probabilities of the mdm2, bcl-2 and androgen receptor expression are different in the tumors with different pathologic types, but statistical difference only consists in androgen receptor expression. (7) No significant association was noted between patient's sex and the expression of mdm2,bcl-2 and androgen receptor in benign meningiomas, a obvious difference was noted, however, in regard to the patient's sex with androgen receptor 36% of males and 50% females expression in all tumors.Conclusions: (1) Meningiomas occur more frequently in women compared with men and develop mostly after or before menopause. This may suggest that meningiomas have a sex hormone link. (2) The change of the ratio between males and females in given occasions and the phenomenon that the proportion of male meningiom patients having a ascending trend going with its pathologic grade may suggest we should give more attention to the effect of the hormone associated with males. (3) The inexistent relationship between mdm2 and bcl-2 found in this study might have some biological and clinical significance. (4) We can consider androgen receptor have a correspondingly independent action in the development of meningioma by the find that no significant relationship exist between androgen receptor and mdm2, bcl-2 in benign meningiomas. Androgen receptor may be a new therapeutic target for meningiomas. (5) Androgen receptor appears positively associated with prognosis as a result of the significant association between tumor pathologic types and androgen receptor expression. (6) The difference of androgen receptor expression in males and females give a hint that androgen receptor act as an important role in the pathogenesis of meningiomas.