Low O6-methylguanine-DNA methyltransferase (MGMT) expression and response to temozolomide in aggressive pituitary tumours.
BACKGROUND
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.


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
McCormack
Ann I
AI
Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia. amccorma@med.usyd.edu.au
McDonald
Kerrie L
KL
Gill
Anthony J
AJ
Clark
Susan J
SJ
Burt
Morton G
MG
Campbell
Kirsten A
KA
Braund
Wilton J
WJ
Little
Nicholas S
NS
Cook
Raymond J
RJ
Grossman
Ashley B
AB
Robinson
Bruce G
BG
Clifton-Bligh
Roderick J
RJ
D000328:Adult; D015331:Cohort Studies; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics* / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000077204:Temozolomide
D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide