title: Prognostic value of MIB-1, p53, epidermal growth factor receptor, and INI1 in childhood chordomas.
abstract: BACKGROUND
  Chordomas are slow-growing tumors and most commonly involve the sacrum and clivus. Multiple recurrences are frequent. Childhood chordomas are rare and often show exceptionally aggressive behavior, resulting in short survival and a high incidence of metastatic spread.
  
  
  OBJECTIVE
  This study examined the histologic features and immunohistochemical profile of pediatric chordomas and compared them with their adult counterparts.
  
  
  METHODS
  Nine pediatric and 13 adult cases were included in the study. Childhood chordomas were classified into conventional, atypical, and poorly differentiated types. Immunohistochemistry was performed for cytokeratin, epithelial membrane antigen, vimentin, S100, brachyury, p53, INI1, epidermal growth factor receptor (EGFR), and CD117. Cytogenetic analyses were performed in a subset of tumors for SMARCB1/INI1 locus on 22q chromosome by fluorescent in situ hybridization (FISH) and analysis of the SMARCB1/INI1 gene sequence.
  
  
  RESULTS
  All tumors showed expression of cytokeratin, epithelial membrane antigen, S100, vimentin, brachyury, and EGFR. Atypical morphology, p53 expression, higher MIB-1 labelling index (LI), and INI1 loss were more frequently seen in pediatric chordomas as compared with adults. None of the tumors showed CD117 expression. No point mutation in the SMARCB1/INI1 gene was noted in the tumors examined; however, 4 pediatric and 1 adult chordoma showed loss of this locus on FISH analysis.
  
  
  CONCLUSIONS
  A subset of pediatric chordomas with atypical histomorphologic features needs to be identified, as they behave in an aggressive manner and require adjuvant therapy. Pediatric chordomas more frequently show p53 expression, INI1 loss, and higher MIB-1 LI as compared with adults, whereas EGFR expression is common to both.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India (R.Y., M.C.S., P.B.M., P.P., E.S., V.S. C.S.); Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India (A.J., M.S., B.S.S.); Department of Neuroradiology, All India Institute of Medical Sciences, New Delhi, India (A.G.); Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India (S.B.).
authors.forename: Rajni
authors.initials: R
authors.lastname: Yadav
authors.forename: Mehar Chand
authors.initials: MC
authors.lastname: Sharma
authors.forename: Prit Benny
authors.initials: PB
authors.lastname: Malgulwar
authors.forename: Pankaj
authors.initials: P
authors.lastname: Pathak
authors.forename: Elanthenral
authors.initials: E
authors.lastname: Sigamani
authors.forename: Vaishali
authors.initials: V
authors.lastname: Suri
authors.forename: Chitra
authors.initials: C
authors.lastname: Sarkar
authors.forename: Amandeep
authors.initials: A
authors.lastname: Kumar
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.forename: Bhawani Shankar
authors.initials: BS
authors.lastname: Sharma
authors.forename: Ajay
authors.initials: A
authors.lastname: Garg
authors.forename: Sameer
authors.initials: S
authors.lastname: Bakhshi
authors.forename: Mohammed
authors.initials: M
authors.lastname: Faruq
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002817:Chordoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors
keywords: EGFR; INI1; chordoma; clivus; pediatric