Endocrine Abstracts (2011) 26 P223

KIT protein expression and mutational status of KIT gene in pituitary adenomas

O Casar-Borota1,2, S L Fougner4,6, J Bollerslev3,6 & J M Nesland3,5

1Department of Laboratory Medicine/Pathology, Umeå University Hospital and Department of Medical Biosciences, Umeå University, Umeå, Sweden; 2Department of Genetics and Pathology, Uppsala University Hospital, Uppsala, Sweden; 3Faculty of Medicine, University of Oslo, Oslo, Norway; 4Research Institute for Internal Medicine, Oslo, Norway; 5Division of Pathology, Oslo University Hospital, Oslo, Norway; 6Section of Specialized Endocrinology, Oslo University Hospital, Oslo, Norway.

Introduction: The proto-oncogene KIT (CD117) is widely expressed in neoplastic tissues. Gain-of-function mutations of the KIT gene were found in some types of leukaemia, gastrointestinal stromal tumours, germinal cell tumours and rarely in other malignancies. Studies on the KIT protein and gene in different tumours have been intensified by the availability of imatinibe mesylate, KIT/PDGFRA inhibitor.

Methods: We have immunohistochemically investigated KIT-expression in 252 pituitary adenomas. Mutational status of exons 9, 11, 13 and 17 of KIT gene has been examined in the tumours with membranous KIT expression and in a minority of tumours with cytoplasmic expression. Detailed clinicopathological correlation was performed for somatotroph adenomas.

Results: 52.4% of adenomas showed cytoplasmic and 8.3% membranous KIT-expression. We found differences in KIT expression between NFPAs, somatotroph and corticotroph adenomas with the highest proportion of adenomas with membranous expression (17.2%) among the somatotropinomas. No mutations in the examined exons were found.

Conclusions: i) The results suggest a pathogenetic role of KIT in a subset of pituitary adenomas. ii) The membranous expression of KIT may thus suggest a potential role for KIT targeting therapy. iii) Despite the high proportion of somatotroph adenomas with membranous expression of KIT in our study, they are probably less attractive candidates for imatinib mesylate therapy due to absence of mutation in the examined exons of KIT, no correlation with clinical data and high proportion of tumours with high sstr2A expression among the KIT-reactive tumours. iv) No mutation in exons 9, 11, 13 and 17 of KIT gene was detected. Search for mutations in other exons of the KIT gene as well as in kinases other than KIT, such as PDGFR would be of interest.

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