Tyrosine kinase receptor expression in chordomas: phosphorylated AKT correlates inversely with outcome

Hum Pathol. 2013 Sep;44(9):1747-55. doi: 10.1016/j.humpath.2012.11.024. Epub 2013 Apr 22.


Chordomas are rare neoplasms arising from notochord remnants. Tyrosine kinase receptors (RTK) are altered in these lesions. We used a tissue microarray containing 58 chordomas to examine the expression of platelet-derived growth factor receptor (PDGFR)-α and PDGFR-β, epidermal growth factor receptor (EGFR), c-Met, c-Kit, pAKT, mammalian target of rapamycin, and HER2 by immunohistochemistry and fluorescence in situ hybridization. Most tumors were positive for PDGFR-α (92%), PDGFR-β (85%), c-Kit (77.4%), c-Met (96%), pAKT (82%), mammalian target of rapamycin (56%), HER2 (24%), and EGFR (26%) by immunohistochemistry. Amplifications or deletions could not be identified for HER2 or EGFR in the 13 cases available for fluorescence in situ hybridization analysis; however, chromosome 7 polysomy was detected in 29% of the cases. The only factor directly associated with a poorer survival rate was pAKT positivity (P = .042). The 5-year survival rate for patients with pAKT-negative chordomas was 100%, whereas it was 45% for patients with pAKT-positive chordomas. Our results confirm that RTKs are frequently altered in chordomas. Given the implications of pAKT positivity, RTK inhibitors might be efficacious, and drugs that inhibit AKT, alone or in combination with radiotherapy, could be an effective treatment for patients with refractory chordomas.

Keywords: Chordoma; EGFR; HER2; Immunohistochemistry; In situ hybridization; PDGFR; Tyrosine kinase receptors; pAKT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aneuploidy
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brazil / epidemiology
  • Child
  • Child, Preschool
  • Chordoma / genetics
  • Chordoma / metabolism*
  • Chordoma / mortality
  • Chordoma / pathology
  • Chromosomes, Human, Pair 7
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Male
  • Middle Aged
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Retrospective Studies
  • Spinal Neoplasms / genetics
  • Spinal Neoplasms / metabolism*
  • Spinal Neoplasms / mortality
  • Spinal Neoplasms / pathology
  • Survival Rate
  • Tissue Array Analysis
  • Young Adult


  • Biomarkers, Tumor
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt