Does insulin-like growth factor 1 receptor (IGF-1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study

• Published in: Histopathology 2012-05, Vol.60 (6), p.999-1003
• Main Authors: Scheipl, Susanne, Froehlich, Elke V, Leithner, Andreas, Beham, Alfred, Quehenberger, Franz, Mokry, Michael, Stammberger, Heinz, Varga, Peter P, Lazáry, Aron, Windhager, Reinhard, Gattenloehner, Stefan, Liegl, Bernadette
• Format: Article
• Language: English
• Subjects: Adult; Age Factors; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - metabolism; brachyury; chordoma; Chordoma - diagnosis; Chordoma - metabolism; Chordoma - mortality; Diseases of the osteoarticular system; Female; Germany - epidemiology; Humans; IGF-1; IGF-1-signalling; IGF-1R; IGF-2; immunohistochemistry; Insulin; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor II - metabolism; Insulin-like growth factors; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Molecular Targeted Therapy; Neoplasm Recurrence, Local; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Prognosis; Receptor, IGF Type 1 - metabolism; Retrospective Studies; Spinal Neoplasms - diagnosis; Spinal Neoplasms - metabolism; Spinal Neoplasms - mortality; survival; Survival Rate; targeted therapies; Tumors of striated muscle and skeleton; Young Adult
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2012.04186.x

Scheipl S, Froehlich E V, Leithner A, Beham A, Quehenberger F, Mokry M, Stammberger H, Varga P P, Lazáry A, Windhager R, Gattenloehner S & Liegl B 
(2012) Histopathology 60, 999–1003 Does insulin‐like growth factor 1 receptor (IGF‐1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study Aims:  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. Methods and 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.