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

Yohei Kitamura, Hikaru Sasaki, Tokuhiro Kimura, Tomoru Miwa, Satoshi Takahashi, Takeshi Kawase, Kazunari Yoshida

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)814-821
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume72
Issue number9
DOIs
Publication statusPublished - 2013 Sep

Fingerprint

Chordoma
Skull Base
Chromosomes
Recurrence
Proportional Hazards Models
Disease-Free Survival
Comparative Genomic Hybridization
Gene Dosage
Brachyury protein
Fluorescence In Situ Hybridization
Genes
Molecular Biology
Neoplasms
Multivariate Analysis
Immunohistochemistry

Keywords

  • Brachyury
  • Chromosome 2p
  • Comparative genomic hybridization
  • Fluorescence in situ hybridization
  • Skull base chordoma
  • T gene

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

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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.",
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AU - Kitamura, Yohei

AU - Sasaki, Hikaru

AU - Kimura, Tokuhiro

AU - Miwa, Tomoru

AU - Takahashi, Satoshi

AU - Kawase, Takeshi

AU - Yoshida, Kazunari

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AB - 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.

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