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Erschienen in: Pituitary 6/2019

30.09.2019

MGMT immunohistochemistry in pituitary tumors: controversies with clinical implications

verfasst von: George Kontogeorgos, Eleni Thodou, Mary Koutourousiou, Gregory Kaltsas, Andreas Seretis

Erschienen in: Pituitary | Ausgabe 6/2019

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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.
Literatur
3.
Zurück zum Zitat O’Reilly SM, Newlands ES, Glaser MG, Brampton M, Rice-Edwards JM, Illingworth RD, Richards PG, Kennard C, Colquhoun IR, Lewis P, Stevens MFG (1993) Temozolomide: a new oral cytotoxic chemotherapeutic agent with promising activity against primary brain tumours. Eur J Cancer 29A:940–942. Erratum in: Eur J Cancer 29A:1500 (1993)CrossRef O’Reilly SM, Newlands ES, Glaser MG, Brampton M, Rice-Edwards JM, Illingworth RD, Richards PG, Kennard C, Colquhoun IR, Lewis P, Stevens MFG (1993) Temozolomide: a new oral cytotoxic chemotherapeutic agent with promising activity against primary brain tumours. Eur J Cancer 29A:940–942. Erratum in: Eur J Cancer 29A:1500 (1993)CrossRef
10.
Zurück zum Zitat Kovacs K, Horvath E, Syro LV, Uribe H, Penagos LC, Ortiz LD, Fadul CE (2007) Temozolomide therapy in a man with an aggressive prolactin-secreting pituitary neoplasm: Morphological findings. Hum Pathol 38:185–189. Erratum in: Hum Pathol 38:526 (2007)CrossRef Kovacs K, Horvath E, Syro LV, Uribe H, Penagos LC, Ortiz LD, Fadul CE (2007) Temozolomide therapy in a man with an aggressive prolactin-secreting pituitary neoplasm: Morphological findings. Hum Pathol 38:185–189. Erratum in: Hum Pathol 38:526 (2007)CrossRef
15.
Zurück zum Zitat Moshkin O, Syro LV, Scheithauer BW, Ortiz LD, Fadul CE, Uribe H, Gonzalez R, Cusimano M, Horvath E, Rotondo F, Kovacs K (2011) Aggressive silent corticotroph adenoma progressing to pituitary carcinoma: the role of temozolomide therapy. Hormones (Athens) 10:162–167. https://doi.org/10.14310/horm.2002.1307 CrossRef Moshkin O, Syro LV, Scheithauer BW, Ortiz LD, Fadul CE, Uribe H, Gonzalez R, Cusimano M, Horvath E, Rotondo F, Kovacs K (2011) Aggressive silent corticotroph adenoma progressing to pituitary carcinoma: the role of temozolomide therapy. Hormones (Athens) 10:162–167. https://​doi.​org/​10.​14310/​horm.​2002.​1307 CrossRef
17.
Zurück zum Zitat McLendon RE, Cleveland L, Pegram C, Bigner SH, Bigner DD, Friedman HS (1998) Immunohistochemical detection of the DNA repair enzyme O6-methylguanine-DNA methyltransferase in formalin-fixed, paraffin-embedded astrocytomas. Lab. Invest. 78:643–644PubMed McLendon RE, Cleveland L, Pegram C, Bigner SH, Bigner DD, Friedman HS (1998) Immunohistochemical detection of the DNA repair enzyme O6-methylguanine-DNA methyltransferase in formalin-fixed, paraffin-embedded astrocytomas. Lab. Invest. 78:643–644PubMed
18.
Zurück zum Zitat Lloyd RV, Kovacs K, Young WF Jr, Farell WE, Asa SL, Touillas J, Kontogeorgos G, Sano T, Scheithauer BW, Horvath E (2004) Pituitary Tumours: Introduction. In: DeLellis RA, Heitz P, Lloyd RV, Eng C (eds) WHO Classification of Tumours, Pathology and Genetics, Tumours of Endocrine Organs. IARC Press, Lyon, pp 10–13 Lloyd RV, Kovacs K, Young WF Jr, Farell WE, Asa SL, Touillas J, Kontogeorgos G, Sano T, Scheithauer BW, Horvath E (2004) Pituitary Tumours: Introduction. In: DeLellis RA, Heitz P, Lloyd RV, Eng C (eds) WHO Classification of Tumours, Pathology and Genetics, Tumours of Endocrine Organs. IARC Press, Lyon, pp 10–13
20.
Zurück zum Zitat Jaffrain-Rea ML (2014) From resistant to aggressive and malignant prolactinomas: a translational approach. J Endocr Disord 1:1–10 Jaffrain-Rea ML (2014) From resistant to aggressive and malignant prolactinomas: a translational approach. J Endocr Disord 1:1–10
21.
Zurück zum Zitat Osamura RY, Lopes MBS, Grossman A, Kontogeorgos G, Trouillas J (2017) Tumours of the pituitary gland. Introduction. In: Lloyd RV, Osamura RV, Klöppel G (eds) WHO classification of tumours of endocrine organs. IARC Press, Lyon Osamura RY, Lopes MBS, Grossman A, Kontogeorgos G, Trouillas J (2017) Tumours of the pituitary gland. Introduction. In: Lloyd RV, Osamura RV, Klöppel G (eds) WHO classification of tumours of endocrine organs. IARC Press, Lyon
24.
Zurück zum Zitat Zuhur SS, Tanik C, Karaman Ö, Velet S, Çil E, Öztürk FY, Özkayalar H, Müslüman AM, Altuntaş Y (2011) MGMT immunoexpression in growth hormone-secreting pituitary adenomas and its correlation with labeling index and cytokeratin distribution pattern. Endocrine 40:222–227CrossRef Zuhur SS, Tanik C, Karaman Ö, Velet S, Çil E, Öztürk FY, Özkayalar H, Müslüman AM, Altuntaş Y (2011) MGMT immunoexpression in growth hormone-secreting pituitary adenomas and its correlation with labeling index and cytokeratin distribution pattern. Endocrine 40:222–227CrossRef
28.
Zurück zum Zitat Bengtsson D, Schrøder HD, Andersen M, Maiter D, Berinder K, Feldt Rasmussen U, Krogh Rasmussen Å, van der Lely A, Petersson M, Johannsson G, Andersen M, Burman P (2015) Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide. J. Clin. Endocrinol. Metab. 100:1689–1698. https://doi.org/10.1210/jc.2014-4350 CrossRefPubMed Bengtsson D, Schrøder HD, Andersen M, Maiter D, Berinder K, Feldt Rasmussen U, Krogh Rasmussen Å, van der Lely A, Petersson M, Johannsson G, Andersen M, Burman P (2015) Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide. J. Clin. Endocrinol. Metab. 100:1689–1698. https://​doi.​org/​10.​1210/​jc.​2014-4350 CrossRefPubMed
30.
Zurück zum Zitat Murakami M, Mizutani A, Asano S, Katakami H, Ozawa Y, Yamazaki K, Ishida Y, Takano K, Okinaga H, Matsuno A (2011) A mechanism of acquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma: case report. Neurosurg. 68:E1761–E1767. https://doi.org/10.1227/NEU.0b013e318217161a CrossRef Murakami M, Mizutani A, Asano S, Katakami H, Ozawa Y, Yamazaki K, Ishida Y, Takano K, Okinaga H, Matsuno A (2011) A mechanism of acquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma: case report. Neurosurg. 68:E1761–E1767. https://​doi.​org/​10.​1227/​NEU.​0b013e318217161a​ CrossRef
Metadaten
Titel
MGMT immunohistochemistry in pituitary tumors: controversies with clinical implications
verfasst von
George Kontogeorgos
Eleni Thodou
Mary Koutourousiou
Gregory Kaltsas
Andreas Seretis
Publikationsdatum
30.09.2019
Verlag
Springer US
Erschienen in
Pituitary / Ausgabe 6/2019
Print ISSN: 1386-341X
Elektronische ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-019-00993-5

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