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MGMT Promoter Methylation and Immunoexpression in Aggressive Pituitary Adenomas and Carcinomas
Author(s) -
Salehi Fateme,
Scheithauer Bernd W,
Kros Johann M,
Lau Queenie,
Fealey Michael,
Syro Luis,
Erickson Dana,
Kovacs Kalman,
Horvath Eva,
Lloyd Ricardo V
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.792.24
MGMT promoter methylation of aggressive pituitary and low protein expression are implicated in improved response to treatment with temozolomide (TMZ). The aim of the present study was to investigate MGMT methylation and immunoexpression in aggressive pituitary adenomas and carcinomas. Our material consisted of 12 silent subtype 3 (SS3) adenomas, 10 carcinomas, and 4 disseminated metastases. Two different samples of 7 of the 12 SS3 adenomas and all carcinomas were analyzed for MGMT methylation and immunoexpression. Overall 33% of carcinomas exhibited homogenous MGMT methylation in tumor and metastatic specimens. Low immunohistochemical MGMT expression was noted in 50% of carcinomas. Overall, 42% of SS3 adenomas exhibited MGMT methylation. MGMT immunostaining was predominantly negative (92%), with homogenous immunostaining results across different samples. Whereas all the methylated SS3 adenomas had low MGMT immunoreactivity, 5 unmethylated adenomas exhibited absent/low MGMT expression. There was no relationship between methylation status and MGMT immunoexpression. MGMT methylation and low immunoexpression was seen in a subset of carcinomas and SS3 adenomas, suggesting some tumors may respond to treatment with TMZ. Heterogeneous MGMT methylation in SS3 adenomas and the lack of concordance between methylation and immunohistochemical expression of MGMT suggest complex regulatory mechanisms.