Low immunohistochemical expression of MGMT in ACTH secreting pituitary tumors of patients with Nelson syndrome.
MGMT expression in tumors has been correlated with response to treatment with temozolomide therapy. Few medical therapies are available for Nelson syndrome, and the efficacy of such therapeutics remains limited. The aim of the present study was to assess immunohistochemical expression of MGMT in ACTH-secreting pituitary adenomas of patients with Nelson syndrome. Our material consisted of eight specimens from ACTH-secreting pituitary adenomas of patients with Nelson syndrome. Immunohistochemical staining for MGMT was performed using the streptavidin-biotin-peroxidase complex method. MGMT immunoreactivity was assessed microscopically and recorded as an estimated percentage of nuclear MGMT immunostaining (0 = none, 1=<10%, 2=<25%, 3=<50%, 4=>50%). Five of the eight specimens (65%) exhibited no MGMT immunoreactivity, with two out of eight cases (25%) showing slight MGMT staining (<10%) and one out of eight cases (12%) demonstrating moderate MGMT positivity (<25%). Patient male/female ratio was 3:5, with average patient age being 62.4 (range 57–66). Our findings suggest that temozolomide therapy may be of potential use in patients with Nelson syndrome, as these tumors express absent/low levels of MGMT. Absent or low MGMT staining in brain and other neoplasms has been shown to correlate with successful treatment with temozolomide, and recent reports of aggressive pituitary adenomas suggest similar outcomes.
Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Fateme
F
Salehi
Bernd W
BW
Scheithauer
Veronica J
VJ
Moyes
William M
WM
Drake
Luis V
LV
Syro
Branavan
B
Manoranjan
Soniya
S
Sharma
Eva
E
Horvath
Kalman
K
Kovacs
D049913:ACTH-Secreting Pituitary Adenoma / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D000236:Adenoma / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D015254:DNA Modification Methylases / Q000096:biosynthesis*; D045643:DNA Repair Enzymes / Q000096:biosynthesis*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009347:Nelson Syndrome / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide