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Low O 6 ‐methylguanine‐DNA methyltransferase (MGMT) expression and response to temozolomide in aggressive pituitary tumours
Author(s) -
McCormack Ann I.,
McDonald Kerrie L.,
Gill Anthony J.,
Clark Susan J.,
Burt Morton G.,
Campbell Kirsten A.,
Braund Wilton J.,
Little Nicholas S.,
Cook Raymond J.,
Grossman Ashley B.,
Robinson Bruce G.,
CliftonBligh Roderick J.
Publication year - 2009
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2008.03487.x
Subject(s) - temozolomide , methyltransferase , o 6 methylguanine dna methyltransferase , immunohistochemistry , dna methyltransferase , methylation , cancer research , dna methylation , pituitary neoplasm , medicine , biology , oncology , chemotherapy , gene expression , pituitary gland , dna , genetics , gene , hormone
Summary Context Recent case reports detail the successful use of temozolomide in the management of aggressive pituitary tumours. O 6 ‐methylguanine‐DNA methyltransferase (MGMT) is a DNA repair protein that counteracts the effect of temozolomide. Objective To study MGMT expression in pituitary tumours and consider whether MGMT expression is associated with response to temozolomide therapy in aggressive pituitary tumours. Patients We report two patients with aggressive pituitary tumours treated with temozolomide, one who responded to temozolomide and the other who did not. MGMT expression was assessed in a further 88 archived pituitary tumour samples. Design MGMT expression was assessed by immunohistochemistry. MGMT promoter methylation was studied by methylation‐specific polymerase chain reaction (MSP), sequencing of MGMT was performed and loss of heterozygosity (LOH) analysis undertaken. Results Low MGMT expression and MGMT promoter methylation were found in the pituitary tumour of the patient who responded to temozolomide. Conversely, high MGMT expression was seen in the patient demonstrating a poor response to temozolomide. Eleven out of 88 archived tumour samples (13%) had low MGMT expression. Prolactinomas were more likely to have low MGMT expression compared with other pituitary tumour subtypes ( P < 0·001). There was no significant difference in MGMT expression between invasive and noninvasive tumours, or between recurrent and nonrecurrent tumours. A significant inverse correlation was found between MGMT expression and promoter methylation ( P = 0·012). Conclusion MGMT expression as assessed by immunohistochemistry may predict response to temozolomide therapy in patients with aggressive pituitary tumours. MGMT promoter methylation is likely to explain low MGMT expression in some, but not all, pituitary tumours.