George Kontogeorgos1,2, Eleni Thodou3, Mary Koutourousiou4, Gregory Kaltsas5, Andreas Seretis6,7. 1. First Propaepeudic Department of Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens, 75 Mikras Asias Str., 11527, Athens, Attica, Greece. gkonto@med.uoa.gr. 2. Department of Pathology, "G. Gennimatas" Athens General Hospital, 154 Messogion Ave., 11527, Athens, Attica, Greece. gkonto@med.uoa.gr. 3. Department of Pathology, School of Medicine, University of Thessaly, Viopolis, 41110, Larissa, Thessaly, Greece. 4. Department of Neurological Surgery, University of Louisville, 220 Abraham Flexner Way, Louisville, KY, 40202, USA. 5. First Propaepeudic Department of Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens, 75 Mikras Asias Str., 11527, Athens, Attica, Greece. 6. Neurosurgery Department, Henry Dunant Hospital, 107 Messogion Ave., 11527, Athens, Attica, Greece. 7. Department of Neurosurgery, "G. Gennimatas" Athens General Hospital, 154 Messogion Ave., 11527, Athens, Attica, Greece.
Abstract
INTRODUCTION: Temozolomide (TMZ) is currently considered as a rational therapeutic option for patients with progressively aggressive pituitary adenomas and carcinomas not responding to conventional therapies. Administration of TMZ results in clinical response and improvement in survival of many of these patients depending upon the expression of the DNA repair enzyme O-6 methylguanine DNA transferase (MGMT). Low or negative MGMT immunoreactivity predicts responsiveness to TMZ therapy. Therefore, MGMT serves as a criterion to select candidate patients anticipating response to treatment. MATERIALS AND METHODS: The MGMT expression was investigated in 25 pituitary adenomas with Ki-67 labeling index more that 3% and p53 expression, using various antigen retrieval protocols. After direct application of the antibody, only one adenoma yielded positive for MGMT. However, after pretreatment of tissue sections with antigen retrieval protocols, another 3 adenomas, initially negative turned to positive. CONCLUSIONS: These findings could explain lack of response to TMZ treatment in patients with false negative MGMT immunohistochemistry. Evaluation of tumor samples for MGMT expression should carefully be carried-out using the optimum immunohistochemical protocol to obtain consistent and reliable results that help to identify patients that could respond to TMZ therapy.
INTRODUCTION:Temozolomide (TMZ) is currently considered as a rational therapeutic option for patients with progressively aggressive pituitary adenomas and carcinomas not responding to conventional therapies. Administration of TMZ results in clinical response and improvement in survival of many of these patients depending upon the expression of the DNA repair enzyme O-6 methylguanine DNA transferase (MGMT). Low or negative MGMT immunoreactivity predicts responsiveness to TMZ therapy. Therefore, MGMT serves as a criterion to select candidate patients anticipating response to treatment. MATERIALS AND METHODS: The MGMT expression was investigated in 25 pituitary adenomas with Ki-67 labeling index more that 3% and p53 expression, using various antigen retrieval protocols. After direct application of the antibody, only one adenoma yielded positive for MGMT. However, after pretreatment of tissue sections with antigen retrieval protocols, another 3 adenomas, initially negative turned to positive. CONCLUSIONS: These findings could explain lack of response to TMZ treatment in patients with false negative MGMT immunohistochemistry. Evaluation of tumor samples for MGMT expression should carefully be carried-out using the optimum immunohistochemical protocol to obtain consistent and reliable results that help to identify patients that could respond to TMZ therapy.
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