Ahead of Print: MGMT Immunohistochemical Expression in Pituitary Corticotroph Adenomas
BACKGROUND: O-6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that counteracts chemotherapeutic cytotoxicity of alkylating agents such as temozolomide. Low levels of MGMT expression have been shown to correlate with longer survival in glioma patients treated with temozolomide. The same is true in pituitary adenomas.
OBJECTIVE: We investigated immunohistochemical expression of MGMT in a variety of corticotroph adenoma subtypes in order to determine the potential utility of temozolomide as a therapeutic agent.
METHODS: The tumors consisted of 40 cases of ACTH-secreting pituitary tumors in Cushing disease, 12 Crooke cell adenomas and 7 subtype I silent corticotroph adenomas. Staining for MGMT was assessed by light microscopy; nuclear reactivity was semiquantitatively estimated as present in <10%, 10-25%, 25-50%, 50-75%, and >75% of cells.
RESULTS: Immunoexpression showed no correlation with patient age, sex, tumor size, invasiveness or recurrence in patients with Cushing disease. Among ACTH-secreting adenomas associated with Cushing disease, most invasive (60%) and recurrent (86%) tumors showed low MGMT immunopositivity, defined as less than 25%. Most (75%) Crooke cell adenomas exhibited an MGMT immunoreactivity of 50% or lower. All subtype I silent corticotroph adenomas showed <10% MGMT staining.
CONCLUSION: Our descriptive findings of low MGMT expression in ACTH-producing pituitary adenomas, particularly aggressive tumors, suggest they may be suitable candidates for temozolomide therapy.