SFEBES2015 Poster Presentations Pituitary (48 abstracts)
Expression of MGMT in a large series of pituitary adenomas: lactotroph and corticotroph adenomas are more likely to be MGMT-negative than somatotroph and gonadotroph adenomas
Danielle A Dixon 1 , Paraskevi Xekouki 1 , Paola Salaris 1 , Omar Mustafa 1 , Julia Prague 1 , Nadeem Abbas 1 , Benjamin Whitelaw 1 , Istvan Bodi 2 & Simon J B Aylwin 1
1Endocrinology, King’s College Hospital, London, SE5 9RS, UK; 2Neuropathology, King’s College Hospital, London, SE5 9RS, UK.
Background: Lack of expression of MGMT (O-6-methylguanine-DNA methyltransferase) is associated with a better tumour response to temozolomide. There are no systematic studies of MGMT expression in pituitary tumour series.
Aim: We introduced MGMT immunohistochemistry for all pituitary adenoma specimens in 2011. In this study we investigated the immunohistochemical expression of MGMT in a large series of pituitary adenomas, in order to determine (1) the overall frequency of expression (2) the relative frequency of MGMT expression according to tumour type and (3) a relation to the proliferative index Ki67.
Methods: We identified a consecutive series of 233 pituitary pathological specimens between 2011 and 2014. MGMT and Ki67 staining were available for 177 patients. MGMT immunohistochemistry was assessed semi-quantitatively as follows: <10% negative, 10–50% intermediate, and >50% strongly positive. Pituitary adenomas with Ki-67 >3% were defined as atypical. The Fisher’s exact test and the χ2-test were used to analyse the association between the types of tumours and MGMT. Correlations between MGMT and Ki-67 expression was assessed by Spearman’s rank correlation analysis.
Results: Among the 177 tumours, 93 (52.5%) were non-functioning (NFPA) and 84 (47.5%) were biochemically active (somatotroph: 32, corticotroph: 24, prolactinoma: 24 and TSHoma: 4). Among NFPAs 81 were gonadotrophs and 12 were immunonegative. MGMT was negative in 17/177 cases (9.6%). Of the negatively stained MGMT tumours, 13/17 (76.47%) were biochemically active and 4/17 NFPAs (23.53%), P=0.039. Corticotroph (25%) and lactotroph adenomas (25%) were more often MGMT negative than gonadotroph (3.7%) or somatotroph adenomas (0%). Overall, no correlation between MGMT and Ki67 staining was detected.
Conclusions: MGMT expression shows tissue specificity in pituitary adenomas. Corticotroph and lactotroph tumours are most likely to be MGMT negative, indicating that temozolomide is most likely to be useful in aggressive ACTH and PRL-secreting tumours.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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