BACKGROUND: Currently, no effective alternative treatment exists for progressive, regrowing, nonfunctioning pituitary adenomas (NFPA) that are resistant to conventional multimodality therapy. Temozolomide (TMZ) was proposed as a treatment option for pituitary carcinomas and aggressive pituitary adenomas. Recently, it was suggested that the responsiveness of pituitary tumors to TMZ depends on the immunoexpression of O(6)-methylguanine DNA methyltransferase (MGMT). Therefore, the authors of this report assessed MGMT expression in a series of patients with progressive, regrowing NFPAs to evaluate whether TMZ may serve as alternative treatment option. METHODS: On the basis of postoperative magnetic resonance imaging, 45 patients with NFPAs were allocated to either a group with progressive, regrowing tumors (n = 24) or a tumor-free group (n = 21), which served as a control. MGMT expression was assessed semiquantitatively by immunohistochemistry (low expression was defined as <or=50% immunostained adenoma cells, and high expression was defined as >50% immunostained adenoma cells) and was compared between the 2 groups. RESULTS: At the time of initial surgery, low MGMT expression was observed in 12 of 24 patients (50%) in the study group with progressive, regrowing NFPAs. In the control group of tumor-free patients, only 5 of 21 patients (24%) exhibited low MGMT expression. A comparable distribution of MGMT expression was observed in the specimens from repeat surgeries. A shorter interval to second surgery was observed in patients who had low MGMT expression. CONCLUSIONS: The current data has suggested that half of the patients with progressive, regrowing NFPAs exhibit low MGMT expression and are potential candidates for treatment with TMZ. These findings provide a rationale for the use of TMZ as an alternative treatment approach in this subgroup if conventional therapy, including reoperation, radiosurgery, and radiotherapy, fails. (c) 2009 American Cancer Society.
BACKGROUND: Currently, no effective alternative treatment exists for progressive, regrowing, nonfunctioning pituitary adenomas (NFPA) that are resistant to conventional multimodality therapy. Temozolomide (TMZ) was proposed as a treatment option for pituitary carcinomas and aggressive pituitary adenomas. Recently, it was suggested that the responsiveness of pituitary tumors to TMZ depends on the immunoexpression of O(6)-methylguanine DNA methyltransferase (MGMT). Therefore, the authors of this report assessed MGMT expression in a series of patients with progressive, regrowing NFPAs to evaluate whether TMZ may serve as alternative treatment option. METHODS: On the basis of postoperative magnetic resonance imaging, 45 patients with NFPAs were allocated to either a group with progressive, regrowing tumors (n = 24) or a tumor-free group (n = 21), which served as a control. MGMT expression was assessed semiquantitatively by immunohistochemistry (low expression was defined as <or=50% immunostained adenoma cells, and high expression was defined as >50% immunostained adenoma cells) and was compared between the 2 groups. RESULTS: At the time of initial surgery, low MGMT expression was observed in 12 of 24 patients (50%) in the study group with progressive, regrowing NFPAs. In the control group of tumor-free patients, only 5 of 21 patients (24%) exhibited low MGMT expression. A comparable distribution of MGMT expression was observed in the specimens from repeat surgeries. A shorter interval to second surgery was observed in patients who had low MGMT expression. CONCLUSIONS: The current data has suggested that half of the patients with progressive, regrowing NFPAs exhibit low MGMT expression and are potential candidates for treatment with TMZ. These findings provide a rationale for the use of TMZ as an alternative treatment approach in this subgroup if conventional therapy, including reoperation, radiosurgery, and radiotherapy, fails. (c) 2009 American Cancer Society.
Authors: A K Annamalai; A F Dean; N Kandasamy; K Kovacs; H Burton; D J Halsall; A S Shaw; N M Antoun; H K Cheow; R W Kirollos; J D Pickard; H L Simpson; S J Jefferies; N G Burnet; M Gurnell Journal: Pituitary Date: 2012-09 Impact factor: 4.107
Authors: Troy H Dillard; S Humayun Gultekin; Johnny B Delashaw; Chris G Yedinak; Edward A Neuwelt; Maria Fleseriu Journal: Pituitary Date: 2011-03 Impact factor: 4.107
Authors: Fateme Salehi; Bernd W Scheithauer; Johann M Kros; Queenie Lau; Michael Fealey; Dana Erickson; Kalman Kovacs; Eva Horvath; Ricardo V Lloyd Journal: J Neurooncol Date: 2011-02-11 Impact factor: 4.130
Authors: Zachary M Bush; Janina A Longtine; Tracy Cunningham; David Schiff; John A Jane; Mary Lee Vance; Michael O Thorner; Edward R Laws; M Beatriz S Lopes Journal: J Clin Endocrinol Metab Date: 2010-07-28 Impact factor: 5.958
Authors: Marie S Thearle; Pamela U Freda; Jeffrey N Bruce; Steven R Isaacson; Yoomi Lee; Robert L Fine Journal: Pituitary Date: 2011-12 Impact factor: 4.107
Authors: Ann McCormack; Warren Kaplan; Anthony J Gill; Nicholas Little; Raymond Cook; Bruce Robinson; Roderick Clifton-Bligh Journal: Pituitary Date: 2013-06 Impact factor: 4.107
Authors: Leon D Ortiz; Luis V Syro; Bernd W Scheithauer; Fabio Rotondo; Humberto Uribe; Camilo E Fadul; Eva Horvath; Kalman Kovacs Journal: Clinics (Sao Paulo) Date: 2012 Impact factor: 2.365