title: Revisiting chordoma with brachyury, a "new age" marker: analysis of a validation study on 51 cases.
abstract: BACKGROUND
  Chordoma is a rare, notochordal tumor with a characteristic histomorphology and immunohistochemical profile. At times, it presents a diagnostic challenge, especially in small biopsies. Brachyury, a nuclear transcription factor, is a recently described immunohistochemical marker for diagnosing chordomas.
  
  
  OBJECTIVE
  To study the sensitivity and specificity of brachyury in diagnosing chordomas by comparing its expression in axial chordomas with nonchordomatous tumors.
  
  
  METHODS
  Fifty-one axial chordomas, accessioned during a 10-year period, and 58 nonchordomatous tumors were subjected to brachyury staining by immunohistochemistry.
  
  
  RESULTS
  The 51 chordomas occurred in 36 men and 15 women. Sitewise, 34 cases (66.7%) occurred in the sacrococcyx, 9 (17.6%) in the spine, and 8 (15.7%) in the skull base. Histologically, 34 cases (66.7%) were classical chordomas, 13 cases (25.5%) had a dominant chondroid component, and 2 cases each (3.9%) were chondroid chordomas and dedifferentiated chordomas, respectively. Brachyury staining was positive in 46 of the 51 chordomas (90.2%) and negative in all 58 nonchordomatous tumors. The dedifferentiated area in 2 chordomas was negative for brachyury staining. Fourteen of 15 chordomas with chondroid component showed positive brachyury staining. Immunohistochemical expression of other markers, included cytokeratin (positive in 23 of 23 cases; 100%), epithelial membrane antigen (positive in 22 of 22 cases; 100%) and S100 protein (positive in 18 of 21 cases; 85.7%).
  
  
  CONCLUSIONS
  Exclusive brachyury expression in more than 90% of chordomas indicates its value as a unique, specific marker with other sensitive markers like cytokeratin, epithelial membrane antigen, and/or S100 protein in substantiating a diagnosis of chordoma, including on small biopsies.
authors.affiliation: Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, India.
authors.forename: Nirmala A
authors.initials: NA
authors.lastname: Jambhekar
authors.forename: Bharat
authors.initials: B
authors.lastname: Rekhi
authors.forename: Kiran
authors.initials: K
authors.lastname: Thorat
authors.forename: Rajesh
authors.initials: R
authors.lastname: Dikshit
authors.forename: Manish
authors.initials: M
authors.lastname: Agrawal
authors.forename: Ajay
authors.initials: A
authors.lastname: Puri
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002817:Chordoma / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D005326:Fetal Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009672:Notochord / Q000378:metabolism / Q000473:pathology*; D019292:Skull Base Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D013125:Spinal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098908:Brachyury Protein
chemical_list: D014408:Biomarkers, Tumor; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein