KIT protein expression and mutational status of KIT gene in pituitary adenomas.
KIT protein expression and mutational status of KIT gene in different types of tumours have been intensively studied since Imatinib Mesylate, KIT/PDGFRA tyrosine kinase inhibitor became available. However, only one immunohistochemical study on KIT expression in pituitary adenomas has been published. There are currently no reports on mutational status of KIT gene in pituitary adenomas. We have immunohistochemically investigated KIT expression in 252 pituitary adenomas and found cytoplasmic reactivity in 52.4% and membranous reactivity in 8.3% of all adenomas. There was statistically significant difference in KIT expression between clinically non-functioning, growth hormone- and adrenocorticotroph hormone-producing adenomas. The group with membranous expression was dominated by somatotropinomas and clinically non-functioning adenomas. KIT expression in a subset of adenomas was also confirmed by western blot analysis of 48 adenomas. Immunohistochemical KIT expression was correlated with basic clinical data and in a cohort of acromegalic patients with additional data (somatostatin receptor type 2A expression, response to somatostatin analogue treatment and mutational status of gsp oncogene). Exons 9, 11, 13 and 17 of KIT gene were searched for mutations in the tumours with membranous KIT expression and in a minority of tumours with cytoplasmic KIT expression using denaturing high-performance liquid chromatography and in suspected cases sequencing of one or more exons. No mutations in the examined exons were found. Our results may suggest a role of KIT in the pathogenesis of a subset of pituitary adenomas and point out the need for further research to find out if KIT-reactive adenomas could be sensitive to Imatinib Mesylate.
Faculty of Medicine, University of Oslo, 0027 Oslo, Norway. olivera.casar.borota@medbio.umu.se
Olivera
O
Casar-Borota
Stine Lyngvi
SL
Fougner
Jens
J
Bollerslev
Jahn Marthin
JM
Nesland
D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics*
D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit