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Expression of a Subset of Steroid Receptor Cofactors Is Associated with Progesterone Receptor Expression in Meningiomas¹

Neurosurgical Laboratories, Brigham and Women’s Hospital, Brain Tumor Center, Brigham and Women’s Hospital, The Children’s Hospital, and Dana Farber Cancer Institute, Department of Surgery, Harvard Medical School [R. S. C., J. Z., P. M. B.], and Department of Medicine, Brigham and Women’s Hospital, and Department of Adult Oncology, Dana-Farber Cancer Institute [M. B., J. D., J. F. D.], Boston, Massachusetts 02115

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.

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