title: Gain of chromosome 7 by chromogenic in situ hybridization (CISH) in chordomas is correlated to c-MET expression.
abstract: Chordomas are low to intermediate grade malignancies that arise from remnants of embryonic notochord. They often recur after surgery and are highly resistant to conventional adjuvant therapies. Recently, the development of effective targeted molecular therapy has been investigated in chordomas that show receptors for tyrosine kinase (RTKs) activation. Expression of specific RTKs such as Epidermal Growth Factor Receptor (EGFR) and Mesenchymal-epithelial transition factor (c-MET) in chordomas may offer valuable therapeutic options. We investigated changes in copy number of chromosome 7 and correlated it with EGFR gene status and EGFR and c-MET protein expression in 22 chordoma samples. Chromosome 7 copy number was evaluated by chromogenic in situ hybridization (CISH) and protein expression of EGFR and c-MET by immunohistochemistry. Tumors mostly showed conventional histopathologic features and were found mainly in sacral (41%) and cranial sites (54.5%). Aneusomy of chromosome 7 was seen in 73% of the samples, 62% of primary tumors and in all recurrent chordomas. EGFR and c-MET were both expressed, but only c-MET protein expression was significantly correlated with chromosome 7 aneusomy (P ≤ 0.001). c-MET overexpression may represent an early chromosome 7 alteration that could play an important role during chordoma pathogenesis. c-MET overexpression shows promise as a molecular marker of response to targeted molecular therapy in the treatment of chordomas.
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10-Magnuson CC, Room 2A10, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Beatriz A
authors.initials: BA
authors.lastname: Walter
authors.forename: Maria
authors.initials: M
authors.lastname: Begnami
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Valera
authors.forename: Mariarita
authors.initials: M
authors.lastname: Santi
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Rushing
authors.forename: Martha
authors.initials: M
authors.lastname: Quezado
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D002817:Chordoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D002897:Chromosomes, Human, Pair 7; D056915:DNA Copy Number Variations / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met