Dexamethasone Suppresses Already Low Estrogen Receptor Levels in Meningiomas

Intracranial meningiomas (ICMs) are the most common primary adult brain tumor. They are more frequent in women, respond to female hormones, are associated with breast cancer and are often progesterone receptor-positive (PR+), consistent with hormonal sensitivity. Yet <20% are weakly estrogen receptor-positive (ER+). This work reviews the literature to investigate this paucity of ER by first testing if Dexamethasone (Dex), which has been used since 1984 to reduce peritumoral brain edema, is suppressing ER. Ligand-binding assays after 1984 have shown a significant decrease in any and supra-threshold (>10 fmol/mg) ER+ from 68.5% and 39.6% to 25.5% and 12%, respectively (both p < 0.0001). This was confirmed as Dex-related in 93 patients with known Dex exposure (p = 0.0075). Immunohistochemical tests after 1984 have shown that 16% (95%CI 8.4-24.4) of ICMs have rare ER+ cells unrelated to PR and pS2 expression, consistent with Dex inhibition of ER transcription activity. Dex suppression of ER may be compounded by lower endogenous ER concentrations in ICMs compared to breast cancer. The difference in intra-tumoral estrogen concentration is proposed as a potential cause for lower ER in ICM. Replacement of Dex and more sensitive ER assays are needed to determine the role of hormones in the causation and treatment of ER+ ICM.