title: O-6-methylguanine-DNA methyltransferase (MGMT) immunohistochemical expression in pituitary corticotroph adenomas.
abstract: 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 the immunohistochemical expression of MGMT in a variety of corticotroph adenoma subtypes to determine the potential utility of temozolomide as a therapeutic agent.
  
  
  METHODS
  The tumors consisted of 40 cases of adrenocorticotropin-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 estimated semiquantitatively as present in < 10%, 10% to 25%, 25% to 50%, 50% to 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 adrenocorticotropin-secreting adenomas associated with Cushing disease, most invasive (60%) and recurrent (86%) tumors showed low MGMT immunopositivity, defined as < 25%. Most (75%) Crooke cell adenomas exhibited an MGMT immunoreactivity of ≤ 50%. All subtype I silent corticotroph adenomas showed < 10% MGMT staining.
  
  
  CONCLUSIONS
  Our descriptive findings of low MGMT expression in adrenocorticotropin-producing pituitary adenomas, particularly aggressive tumors, suggest that they may be suitable candidates for temozolomide therapy.
authors.affiliation: Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Fateme
authors.initials: F
authors.lastname: Salehi
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Scheithauer
authors.forename: Kalman
authors.initials: K
authors.lastname: Kovacs
authors.forename: Eva
authors.initials: E
authors.lastname: Horvath
authors.forename: Luis V
authors.initials: LV
authors.lastname: Syro
authors.forename: Soniya
authors.initials: S
authors.lastname: Sharma
authors.forename: Branavan
authors.initials: B
authors.lastname: Manoranjan
authors.forename: Michael
authors.initials: M
authors.lastname: Cusimano
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D015254:DNA Modification Methylases / Q000032:analysis / Q000096:biosynthesis*; D045643:DNA Repair Enzymes / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes