title: Molecular and clinical risk factors for recurrence of skull base chordomas: gain on chromosome 2p, expression of brachyury, and lack of irradiation negatively correlate with patient prognosis.
abstract: Chordomas are invasive tumors that develop from notochordal remnants and frequently occur in the skull base. The T gene and its product (brachyury) have recently been suggested to play an important role in chordoma progression. To date, few studies have investigated the relationship between the molecular/genetic characteristics of chordoma and patient prognosis. We analyzed 37 skull base chordomas for chromosomal copy number aberrations using comparative genomic hybridization, brachyury expression by immunohistochemistry, and T gene copy number by fluorescence in situ hybridization. The results of these molecular analyses and clinical parameters were compared with the patients' clinical courses. Univariate analyses using the log-rank test demonstrated that losses on chromosome 1p and gains on 1q and 2p were negatively correlated with progression-free survival, as were factors such as female sex, partial tumor removal, lack of postoperative irradiation, and high MIB-1 index. Expression of brachyury and copy number gain of the T gene were also significantly associated with shorter progression-free survival. Multivariate analysis using the Cox hazards model showed that lack of irradiation, gain on chromosome 2p, and expression of brachyury were independently associated with a poor prognosis. Our results suggest that brachyury-negative chordomas arebiologically distinct from brachyury-positive chordomas and that T/brachyury might be an appropriate molecular therapeutic target for chordoma.
authors: Departments of Neurosurgery, and Pathology, Keio University School of Medicine, Tokyo, Japan.
authors: Yohei
authors: Y
authors: Kitamura
authors: Hikaru
authors: H
authors: Sasaki
authors: Tokuhiro
authors: T
authors: Kimura
authors: Tomoru
authors: T
authors: Miwa
authors: Satoshi
authors: S
authors: Takahashi
authors: Takeshi
authors: T
authors: Kawase
authors: Kazunari
authors: K
authors: Yoshida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002817:Chordoma / Q000175:diagnosis / Q000235:genetics / Q000532:radiotherapy; D002869:Chromosome Aberrations; D002889:Chromosomes, Human, Pair 2; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D019292:Skull Base Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000532:radiotherapy; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein