Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas

• Published in: The Journal of pathology Vol. 209; no. 2; pp. 157 - 165
• Main Authors: Vujovic, S, Henderson, S, Presneau, N, Odell, E, Jacques, TS, Tirabosco, R, Boshoff, C, Flanagan, AM
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-06-2006; Wiley
• Subjects: Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; brachyury; Cartilage Diseases - diagnosis; Cartilage Diseases - genetics; chondrosarcoma; Chondrosarcoma - diagnosis; Chondrosarcoma - embryology; Chondrosarcoma - genetics; chordoma; Chordoma - diagnosis; Chordoma - embryology; Chordoma - genetics; Diseases of the osteoarticular system; Fetal Proteins - analysis; Fetal Proteins - genetics; Gene Expression Regulation, Neoplastic - genetics; Humans; Immunohistochemistry - methods; Investigative techniques, diagnostic techniques (general aspects); Keratins - analysis; Keratins - genetics; Medical sciences; notochord; Notochord - chemistry; Notochord - embryology; nucleus pulposus; parachordoma; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Reverse Transcriptase Polymerase Chain Reaction - methods; Spinal Neoplasms - diagnosis; Spinal Neoplasms - embryology; Spinal Neoplasms - genetics; T-Box Domain Proteins - analysis; T-Box Domain Proteins - genetics; Tissue Distribution; Tumors of striated muscle and skeleton; Chondrosarcoma; Sarcoma; Diseases of the osteoarticular system; Biological marker; Biological indicator; notochord; Malignant tumor; Nucleus pulposus; Regulator; brachyury; Osteoarticular system; Cartilage; Chordoma; Anatomic pathology; Development; parachordoma; Bone
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.1969

Chordomas are malignant tumours that occur along the spine and are thought to derive from notochordal remnants. There is significant morphological variability between and within chordomas, with some showing prominent areas of chondroid differentiation. Our microarray data from a broad range of connective tissue neoplasms indicate that, at the transcriptional level, chordomas resemble cartilaginous neoplasms. Here we show that chordomas express many genes known to be involved in cartilage development, but they also uniquely express genes distinguishing them from chondroid neoplasms. The brachyury transcription factor, known to be involved in notochordal development, is only expressed by chordomas. Using a polyclonal antibody, we show that brachyury is expressed in the embryonic notochord and in all 53 chordomas analysed, labelling both chondroid and chordoid areas of these tumours. In contrast, the protein was not detected in over 300 neoplasms, including 163 chondroid tumours. Brachyury was not detected in the nucleus pulposus, arguing against the hypothesis that this tissue derives directly from the notochord. These data provide compelling evidence that chordomas derive from notochord and demonstrate that brachyury is a specific marker for the notochord and notochord‐derived tumours. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.