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Published on: January 9, 2019
MGMT immunoexpression in growth hormone-secreting pituitary adenomas and its correlation with Ki-67 labeling index
Sayid Shafi Zuhur1, Canan Tanik, Özcan Karaman
1Endocrinology and Metabolism Clinic, Sisli Etfal Training and Research Hospital, 34377 Sisli, Istanbul, Turkey. zuhur744@gmail.com
Abstract:
Recent publications suggest the utility of temozolomide (TMZ) in the management of aggressive pituitary adenomas and carcinomas, resistant to conventional treatments. The response to TMZ is inversely correlated with tumoral expression of O-6 methylguanine DNA methyl transferase (MGMT). Therefore, we aimed to assess MGMT immunoexpression in pure GH-secreting pituitary adenomas, in an effort to predict the likelihood of response to TMZ, and to correlate MGMT immunoexpression with Ki-67 LI and cytokeratin (CK) distribution pattern. 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 MGMT, Ki-67, and CK was performed using avidin-biotin-peroxidase complex method. Immunoreactivity for MGMT and Ki-67 was evaluated microscopically and recorded as percentages of positive nuclear immunostaining. CK distribution pattern was also evaluated microscopically and assoreted into dot-like and nondot-like pattern subtypes. MGMT immunoexpression scored as 0=none, 1=<10%, 2=<25%, 3=<50%, and 4=>50%. 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 was no correlation between Ki-67 LI and CK distribution pattern with MGMT immunoreactivity (P>0.05). Data from the current study suggest a large proportion of GH-secreting adenomas, including those with dot-like CK distribution pattern and high Ki-67 LI, demonstrate negative/low MGMT immunoreactivity and could be treated with TMZ, if conventional treatment fails.
Insights
Temozolomide (TMZ) shows promise for aggressive pituitary tumors. Most GH-secreting adenomas exhibit low O-6 methylguanine DNA methyl transferase (MGMT) expression, suggesting potential TMZ efficacy when conventional treatments fail.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Temozolomide (TMZ) is emerging as a treatment for aggressive pituitary adenomas and carcinomas.
- Tumor response to TMZ correlates inversely with O-6 methylguanine DNA methyl transferase (MGMT) expression.
Purpose of the Study:
- To evaluate MGMT immunoexpression in GH-secreting pituitary adenomas.
- To predict the potential response to TMZ therapy.
- To correlate MGMT expression with Ki-67 labeling index (LI) and cytokeratin (CK) distribution patterns.
Main Methods:
- Analysis of 36 GH-secreting pituitary adenomas using immunostaining for MGMT, Ki-67, and CK.
- Microscopic evaluation of MGMT and Ki-67 nuclear immunostaining percentages.
- Classification of CK distribution into dot-like and nondot-like patterns.
Main Results:
- A high proportion (83.3%) of tumors showed low MGMT immunoexpression (<10%).
- No significant correlation was found between MGMT immunoreactivity and Ki-67 LI or CK distribution patterns (P>0.05).
Conclusions:
- GH-secreting pituitary adenomas frequently exhibit low MGMT expression, indicating potential sensitivity to TMZ.
- TMZ may be a viable treatment option for these tumors, particularly when conventional therapies are ineffective.
