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

Scheipl S, Froehlich E V, Leithner A, Beham A, Quehenberger F, Mokry M, Stammberger H, Varga P P, Lazary 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.