title: Does insulin-like growth factor 1 receptor (IGF-1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study.
abstract: OBJECTIVE
  The overall prognosis of chordoma is poor, and current treatment options are limited. The insulin-like growth factor 1 receptor (IGF-1R) pathway is important for cell signalling, and attractive for selective inhibition. We investigated the expression of IGF-1R and its ligands, IGF-1 and IGF-2, in a series of 50 chordomas, in order to assess whether IGF-1R-signalling could be a potential target for specific inhibition in chordomas.
  
  
  RESULTS
  Fifty chordomas (34 primary tumours, 16 recurrences) from 44 patients were evaluated immunohistochemically for the expression of IGF-1R, IGF-1 and IGF-2. Thirty-eight chordomas (76%) expressed IGF-1R, 46 (92%) expressed IGF-1 and 25 (50%) expressed IGF-2. Semi-quantitative analyses revealed a moderate to strong staining intensity in ≥ 50% of tumour cells for IGF-1R, IGF-1 and IGF-2 in 18 (36%), 32 (64%) and eight (16%) chordomas, respectively. Tumour volume correlated significantly with IGF-1R-staining intensity in primary chordomas (P = 0.042).
  
  
  CONCLUSIONS
  IGF-1R and IGF-1 are expressed in the majority of chordomas. IGF-1 expression is much stronger than IGF-2 expression. Patients whose chordomas show a moderate to strong staining intensity in ≥ 50% of tumour cells for IGF-1R (36%) might benefit most from IGF-1R targeting, particularly if they suffer from large and surgically non-resectable chordomas.
authors.affiliation: Department of Orthopaedics and Orthopaedic Surgery, Medical University of Graz, Graz, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Scheipl
authors.forename: Elke V
authors.initials: EV
authors.lastname: Froehlich
authors.forename: Andreas
authors.initials: A
authors.lastname: Leithner
authors.forename: Alfred
authors.initials: A
authors.lastname: Beham
authors.forename: Franz
authors.initials: F
authors.lastname: Quehenberger
authors.forename: Michael
authors.initials: M
authors.lastname: Mokry
authors.forename: Heinz
authors.initials: H
authors.lastname: Stammberger
authors.forename: Peter P
authors.initials: PP
authors.lastname: Varga
authors.forename: Aron
authors.initials: A
authors.lastname: Lazáry
authors.forename: Reinhard
authors.initials: R
authors.lastname: Windhager
authors.forename: Stefan
authors.initials: S
authors.lastname: Gattenloehner
authors.forename: Bernadette
authors.initials: B
authors.lastname: Liegl
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002817:Chordoma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012189:Retrospective Studies; D013125:Spinal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1