Expression of platelet-derived growth factor-alpha receptor and c-kit in giant cell tumours of bone.
OBJECTIVE
Platelet-derived growth factor-alpha receptor (PDGFRA) and c-kit are tyrosine kinase receptors expressed in many neoplasms. We investigated protein expression in 34 giant cell tumours of bone and two specimens of lung metastases.


METHODS
The expression of PDGFRA and c-kit was analysed by immunohistochemistry. Additionally, capillary sequencing of genomic DNA was performed to search for mutations in therapeutically relevant exons 12 and 18 of the PDGFRA gene and exons 9 and 11 of the c-kit gene.


RESULTS
PDGFRA expression was detected in all specimens and all cellular components such as reactive osteoclast-like giant cells and neoplastic stromal cells. C-kit expression was found in six cases of giant cell tumour and one specimen of lung metastasis in all cellular components ranging from 5 to 50% (mean 4.8%, SD 12.4). A further 13 cases showed labelling of osteoclast-like giant cells. DNA sequence of exons 12 and 18 of the PDGFRA gene and exons 9 and 11 of the c-kit gene were not altered in these tumours.


CONCLUSIONS
PDGFRA and c-kit play a functional role in the growth of giant cell tumours of bone but genetic changes of therapeutically relevant exons of the PDGFRA gene and the c-kit gene are not seen in these tumours.
Sulzbacher
Irene
I
Institute of Pathology, Medical University of Vienna, Vienna, Austria. irene.sulzbacher@meduniwien.ac.at
Dominkus
Martin
M
Pichlhofer
Bettina
B
Mazal
Peter R
PR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018212:Giant Cell Tumor of Bone / Q000378:metabolism* / Q000556:secondary; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D055815:Young Adult
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha