MET overexpressing chordomas frequently exhibit polysomy of chromosome 7 but no MET activation through sarcoma-specific gene fusions.
Overexpression of MET and polysomy 7 was formerly demonstrated in chordomas. We investigated mesenchymal-epithelial transition factor (MET) protein expression and copy numbers of chromosome 7 in human chordomas. Furthermore, tumors were screened for gene fusions (PAX3-FKHR, ASPL-TFE3, and SYT-SSX) previously shown to be associated with MET activation in sarcomas. Tissue microarrays (TMAs) were constructed from 66 chordoma samples. MET protein expression was assessed by immunohistochemistry using an immunoreactive score (IRS, scores 0-12). fluorescence in situ hybridization (FISH) with a dual-color DNA probe (7q31) for MET amplification was performed on TMA sections and RT-PCR for PAX3-FKHR, ASPL-TFE3 (type 1 + 2), and SYT-SSX (type 1 + 2) gene fusions on punch biopsies. All tumors (n = 66) expressed MET protein. FISH analysis of 33 tumors lacked MET gene amplification but showed polysomy of chromosome 7 in 15 (45.5%) tumors (13 low and two high polysomies). Although, polysomy 7 showed an increasing incidence with escalating MET IRS, this finding was not statistically significant. PAX3-FKHR, ASPL-TFE3, or SYT-SSX gene fusions were not demonstrable (n = 52). We found MET protein expression in all chordomas. A clear influence of polysomy 7 on MET protein expression could not be statistically demonstrated for this cohort. Moreover, gene fusions with the ability to cause MET overexpression do not occur in chordomas.
Grabellus
Florian
F
Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany. florian.grabellus@uk-essen.de
Konik
Margarethe J
MJ
Worm
Karl
K
Sheu
Sien-Yi
SY
van de Nes
Johannes A P
JA
Bauer
Sebastian
S
Paulus
Werner
W
Egensperger
Rupert
R
Schmid
Kurt W
KW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002648:Child; D002817:Chordoma / Q000235:genetics* / Q000378:metabolism; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D050939:Gene Fusion; D006801:Humans; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D019859:Proto-Oncogene Proteins c-met