Temozolomide Treatment for Aggressive Pituitary Tumors: Correlation of Clinical Outcome with O6-Methylguanine Methyltransferase (MGMT) Promoter Methylation and Expression

被引:116
作者
Bush, Zachary M. [2 ]
Longtine, Janina A. [3 ]
Cunningham, Tracy [4 ]
Schiff, David [5 ]
Jane, John A., Jr. [6 ]
Vance, Mary Lee [2 ]
Thorner, Michael O. [2 ]
Laws, Edward R., Jr. [7 ]
Lopes, M. Beatriz S. [1 ]
机构
[1] Univ Virginia, Div Neuropathol, Dept Pathol, Charlottesville, VA 22908 USA
[2] Univ Virginia, Div Endocrinol & Metab, Charlottesville, VA 22908 USA
[3] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[4] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA
[5] Univ Virginia, Div Neurooncol, Charlottesville, VA 22908 USA
[6] Univ Virginia, Dept Neurosurg, Charlottesville, VA 22908 USA
[7] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA
关键词
GLIOBLASTOMA-MULTIFORME; TRANSSPHENOIDAL SURGERY; ADJUVANT TEMOZOLOMIDE; CUSHINGS-DISEASE; DNA METHYLATION; CARCINOMA; ADENOMAS; THERAPY; HYPERMETHYLATION; RADIOTHERAPY;
D O I
10.1210/jc.2010-0441
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: The typically indolent behavior of pituitary tumors is juxtaposed with high rates of tumor cell invasion into adjacent dural structures, and occasional aggressive behavior. Although clinically significant invasion and malignant transformation remain uncommon, there are limited treatment options available for the management of these aggressive tumors. Recently, case reports have described efficacy of temozolomide for the treatment of aggressive pituitary tumors. Design: Seven patients with aggressive pituitary tumors have been treated with temozolomide. We compared O-6-methylguanine methyltransferase (MGMT) promoter methylation and MGMT expression in 14 surgical specimens from these seven patients and correlated these molecular features with the clinical response to temozolomide. Results: Significant tumor regression was seen in two patients (29%), a 20% reduction in tumor volume with subsequent stable tumor size was noted in one patient, arrest of tumor growth occurred in three patients, and progressive metastatic disease developed during treatment in one patient. The DNA promoter site for MGMT was unmethylated in all 14 adequate specimens, and variable MGMT expression was seen in all 14 cases. There was no correlation between MGMT expression and clinical outcomes. Conclusions: We conclude that medical therapy with temozolomide can be helpful in the management of life-threatening pituitary tumors that have failed to respond to conventional treatments. The optimal duration of treatment in patients with stabilization or reduction of tumor size has not been established, and long-term follow up studies are needed. (J Clin Endocrinol Metab 95: E280-E290, 2010)
引用
收藏
页码:E280 / E290
页数:11
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