The Black Laboratory, Meningioma Research

Steroid Cofactor Expression

Expression of a subset of steroid receptor cofactors is associated with progesterone receptor expression in meningiomas
The predominance of meningiomas in females, their accelerated growth during the luteal phase of the menstrual cycle and during pregnancy, and the association between meningiomas and breast cancer have led to a number of studies examining the potential role of steroids on the growth of meningiomas. There are numerous discrepancies in the literature about the mitogenic effects of steroids on meningiomas in both in vitro and in vivo models. The aim of this study was to examine the expression of three steroid receptor coactivators, along with progesterone receptor and estrogen receptor in meningiomas. This additional regulatory layer may explain the heterogeneity of hormone responses observed in these tumors. Using Western blot analysis and immunohistochemistry, we demonstrate the expression of the steroid coactivators steroid receptor cofactor (SRC-1), amplified in breast cancer protein (AIB1), and transcriptional intermediary factor 2 (TIF2) in 81, 76, and 76% of meningiomas, respectively. The expression of SRC-1 and TIF2 is significantly related to progesterone but not to estrogen receptor expression. In contrast, seven normal brain specimens were positive for TIF2 and SRC-1 but negative for AIB1. One leptomeningeal specimen was positive for AIB1, SRC-1, and progesterone receptor. The differential expression of steroid receptor coactivators may explain the differential response of these tumors to hormonal therapy.

Carroll RS, Brown M, Zhang J, DiRenzo J, Font de Mora, J, Black PM. Expression of a Subset of Steroid Receptor Cofactors is Associated with Progesterone Receptor Expression in Meningiomas . Clin Cancer Res, 6(9): 3570-3575, 2000.

Reproductive and hormonal factors and risk of brain tumors in adult females
Causes of brain tumors are largely unknown, and there is an urgent need to identify possible risk factors. Several observations point to a possible role of reproductive hormones, but few epidemiologic studies have examined whether reproductive factors, such as age at menarche and parity, are associated with brain tumor risk. We conducted a multi-center case-control study of newly diagnosed glioma (n = 212) and meningioma (n = 151) and frequency-matched controls (n = 436) in women from hospitals in Phoenix, Arizona; Boston, Massachusetts; and Pittsburgh, Pennsylvania between 1994 and 1998. Research nurses interviewed patients regarding potential risk factors for brain tumors, including reproductive factors and hormone use. Unconditional logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Risk of glioma increased with older age at menarche [OR = 1.90 (95% CI = 1.09-3.32) for age at menarche > or =14 vs. <12 years]. Early age at first birth was associated with reduced risk of glioma [OR = 0.43 (95% CI = 0.23-0.83) for a first birth before age 20 vs. nulliparity], but there was little effect of number of births. Exogenous hormone use was also associated with a lower risk of glioma, but risks did not vary systematically according to duration of use or age at first use. Possibly owing to low statistical power, there were few noteworthy associations between meningioma and reproductive factors, other than a nonsignificant (p = 0.09) trend of increasing risk with increasing age at menopause. The findings suggest that hormonal exposures early in life may be associated with risk of glioma, but the evidence is inconsistent and does not point clearly to a specific causal or protective hypothesis. 2004 Wiley-Liss, Inc.

Hatch EE, Linet MS, Zhang J, Fine HA, Shapiro WR, Selker RG, Black PM, Inskip PD. Reproductive and Hormonal Factors and Risk of Brain Tumors in Adult Females . Int J Cancer. 114(5): 797-805, 2005.