title: MGMT immunoexpression in silent subtype 3 pituitary adenomas: possible therapeutic implications.
abstract: The objective of the study was to assess O(6)-methylguanine-DNA methyltransferase (MGMT) immunoreactivity in pituitary adenomas of silent subtype 3 as a potential indicator of temozolomide susceptibility. The Mayo Clinic Anatomic Pathology Database was searched for all cases of silent subtype 3 pituitary adenoma. Each of the 23 cases identified had been confirmed on the basis of histology, immunohistochemical staining for pituitary hormones, as well as on diagnostic ultrastructural criteria. Unstained microscopic sections were immunostained for MGMT and were semiquantitatively assessed. Of the 23 tumors examined, 18 (78%) showed no MGMT immunoreactivity. The remaining five (22%) showed immunoreactivity in < or =50% of tumor cells. Among eight of the most clinically aggressive tumors in this study, six (75%) lacked MGMT immunoreactivity. The observed lack of or low-level expression of MGMT by this distinctive, clinically aggressive form of pituitary adenoma suggests potential efficacy of treatment with the alkylating agent temozolomide.
authors.affiliation: Mayo Work Study Program, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Fealey
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Scheithauer
authors.forename: Eva
authors.initials: E
authors.lastname: Horvath
authors.forename: Dana
authors.initials: D
authors.lastname: Erickson
authors.forename: Kalman
authors.initials: K
authors.lastname: Kovacs
authors.forename: Roger
authors.initials: R
authors.lastname: McLendon
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Lloyd
mesh_terms: D000236:Adenoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000096:biosynthesis* / Q000235:genetics; D045643:DNA Repair Enzymes / Q000096:biosynthesis* / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide