Endocrine Abstracts (2011) 26 P206

O-6 methylguanine-DNA methyl transferase (MGMT) immunoexpression in GH secreting pituitary adenomas and it's correlation with Ki-67 labeling index (Ki-67 LI)

Sayid Shafi Zuhur1, Canan Tanik2, Ozcan Karaman1, Esra Cil1, Selvinaz Velet1, Feyza Yener Ozturk1, Ahmet Murat Musluman3 & Yuksel Altuntas1

1Sisli Etfal Training and Research Hospital, Endocrinology and Metabolism Clinic, Istanbul, Turkey; 2Sisli Etfal Training and Rsearch Hospital, Pathology Clinic, Istanbul, Turkey; 3Sisli Etfal Training and Research Hospital, Neurosurgery Clinic, Istanbul, Turkey.

Background: Currently, multiple treatment options are available for the treatment of acromegaly. However, cure is obtained only in 50% of patients with macroadenomas after surgery. Persistent tumor enlargement occur in 2.2% of the patients treated with somatostatin analogs and in 1.6–2.9% of the patients treated with pegvisomant. The nuclear antigen Ki-67 is related to growth potential and is also a major prognostic indicator for pituitary adenomas. Studies demonstrated that, the mean Ki-67 LI was high in invasive tumors that could not be cured by surgery. Tumors with high Ki-67 LI are also less responsive to somatostatin analogs. Recent reports suggest the utility of temozolomide in the management of aggressive pituitary adenomas and carcinomas, resistant to conventional treatments. The response to temozolomide is inversely correlated with tumoral expression of MGMT.

Purpose: To evaluate MGMT immunoexpression in GH secreting pituitary adenomas, in an effort to predict the likelihood of response to TMZ, and to correlate MGMT immunoexpression with Ki-67 LI.

Methods: 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 Ki-67 and MGMT was performed using avidin–biotin–peroxidase complex method. Immunoreactivity was evaluated microscopically and recorded as percentage of nuclear Ki-67 and MGMT immunostaining. MGMT immunoexpression scored as 0=none, 1=<10%, 2=<25%, 3=<50%, 4=>50%.

Results: 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 is no correlation between Ki-67 LI with MGMT immunorectivity (P>0.05).

Conclusion: Our data suggests that more than 90% of GH secreting pituitary adenomas express negative/low MGMT. Despite high Ki-67 LI, most of these patients may respond to TMZ, if conventional treatment fails.

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