title: MGMT immunoexpression in growth hormone-secreting pituitary adenomas and its correlation with Ki-67 labeling index and cytokeratin distribution pattern.
abstract: Recent publications suggest the utility of temozolomide (TMZ) in the management of aggressive pituitary adenomas and carcinomas, resistant to conventional treatments. The response to TMZ is inversely correlated with tumoral expression of O-6 methylguanine DNA methyl transferase (MGMT). Therefore, we aimed to assess MGMT immunoexpression in pure GH-secreting pituitary adenomas, in an effort to predict the likelihood of response to TMZ, and to correlate MGMT immunoexpression with Ki-67 LI and cytokeratin (CK) distribution pattern. Our material consisted of 36 GH-secreting pituitary adenomas (21 female,15 male, mean age 42.5±10.5), operated at our center between 2003 and 2010. Immunostaining for MGMT, Ki-67, and CK was performed using avidin-biotin-peroxidase complex method. Immunoreactivity for MGMT and Ki-67 was evaluated microscopically and recorded as percentages of positive nuclear immunostaining. CK distribution pattern was also evaluated microscopically and assoreted into dot-like and nondot-like pattern subtypes. MGMT immunoexpression scored as 0=none, 1=<10%, 2=<25%, 3=<50%, and 4=>50%. Staining for MGMT was <10% (score 1) in 30 (83.3%), 10-25% (score 2) in 3 (8.3%), 25-50% (score 3) in 2 (5.6%) and >50% (score 4) in 1 (2.8%) of the tumors, respectively. There was no correlation between Ki-67 LI and CK distribution pattern with MGMT immunoreactivity (P>0.05). Data from the current study suggest a large proportion of GH-secreting adenomas, including those with dot-like CK distribution pattern and high Ki-67 LI, demonstrate negative/low MGMT immunoreactivity and could be treated with TMZ, if conventional treatment fails.
authors.affiliation: Endocrinology and Metabolism Clinic, Sisli Etfal Training and Research Hospital, 34377 Sisli, Istanbul, Turkey. zuhur744@gmail.com
authors.forename: Sayid Shafi
authors.initials: SS
authors.lastname: Zuhur
authors.forename: Canan
authors.initials: C
authors.lastname: Tanik
authors.forename: Özcan
authors.initials: Ö
authors.lastname: Karaman
authors.forename: Selvinaz
authors.initials: S
authors.lastname: Velet
authors.forename: Esra
authors.initials: E
authors.lastname: Çil
authors.forename: Feyza Yener
authors.initials: FY
authors.lastname: Öztürk
authors.forename: Hanife
authors.initials: H
authors.lastname: Özkayalar
authors.forename: Ahmet Murat
authors.initials: AM
authors.lastname: Müslüman
authors.forename: Yüksel
authors.initials: Y
authors.lastname: Altuntaş
mesh_terms: D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D019382:Human Growth Hormone; D007633:Keratins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide