Grabellus Florian, Konik Margarethe J, Worm Karl, Sheu Sien-Yi, van de Nes Johannes A P, Bauer Sebastian, Paulus Werner, Egensperger Rupert, Schmid Kurt W
Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
Tumour Biol. 2010 Jun;31(3):157-63. doi: 10.1007/s13277-010-0021-0. Epub 2010 Mar 6.
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.
MET的过表达和7号染色体多体性先前已在脊索瘤中得到证实。我们研究了人间脊索瘤中膜上皮转化因子（MET）蛋白表达及7号染色体的拷贝数。此外，对肿瘤进行筛查，寻找先前已证实在肉瘤中与MET激活相关的基因融合（PAX3-FKHR、ASPL-TFE3和SYT-SSX）。用66例脊索瘤样本构建组织微阵列（TMA）。采用免疫反应评分（IRS，0 - 12分）通过免疫组织化学评估MET蛋白表达。在TMA切片上用双色DNA探针（7q31）进行荧光原位杂交（FISH）检测MET扩增情况，并在穿刺活检样本上进行PAX3-FKHR、ASPL-TFE3（1型 + 2型）和SYT-SSX（1型 + 2型）基因融合的逆转录聚合酶链反应（RT-PCR）。所有肿瘤（n = 66）均表达MET蛋白。对33例肿瘤进行FISH分析，未发现MET基因扩增，但15例（45.5%）肿瘤显示7号染色体多体性（13例低多体性和2例高多体性）。尽管7号染色体多体性随MET IRS升高而发生率增加，但这一发现无统计学意义。未检测到PAX3-FKHR、ASPL-TFE3或SYT-SSX基因融合（n = 52）。我们发现所有脊索瘤均有MET蛋白表达。对于该队列，无法从统计学上证实7号染色体多体性对MET蛋白表达有明显影响。此外，脊索瘤中未出现具有导致MET过表达能力的基因融合。
