MET overexpressing chordomas frequently exhibit polysomy of chromosome 7 but no MET activation through sarcoma-specific gene fusions
- 156 Downloads
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.
KeywordsMET protooncogene Chordoma PAX3-FKHR SYT-SSX ASPL-TFE3
This study was supported by grants from the IFORES-program of the Faculty of Medicine of the University of Duisburg-Essen (IFORES 107-20360 to F. G.).
The authors wish to acknowledge the excellent and enthusiastic technical assistance of Nicole Cramer, Gabriele Ladwig, and Andrea Kutritz.
The authors certify that there is no actual or potential conflict of interest in relation to this article.
- 16.Wallenius V, Hisaoka M, Helou K, Levan G, Mandahl N, Meis-Kindblom JM, et al. Overexpression of the hepatocyte growth factor (HGF) receptor (Met) and presence of a truncated and activated intracellular HGF receptor fragment in locally aggressive/malignant human musculoskeletal tumors. Am J Pathol. 2000;156:821–9.PubMedGoogle Scholar
- 23.Nascimento AG. World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone. Lyon: IARCPress; 2002.Google Scholar
- 31.Downs-Kelly E, Yoder BJ, Stoler M, Tubbs RR, Skacel M, Grogan T, et al. The influence of polysomy 17 on HER2 gene and protein expression in adenocarcinoma of the breast: a fluorescent in situ hybridization, immunohistochemical, and isotopic mRNA in situ hybridization study. Am J Surg Pathol. 2005;29:1221–7.CrossRefPubMedGoogle Scholar
- 32.Binh MB, Sastre-Garau X, Guillou L, de Pinieux G, Terrier P, Lagace R, et al. MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data. Am J Surg Pathol. 2005;29:1340–7.CrossRefPubMedGoogle Scholar