Chordomas are rare, locally aggressive
malignancies that often exhibit an insidious natural history and are difficult to eradicate. Surgery and
radiotherapy are the treatment mainstays of
chordoma, but the chance of local recurrence remains high. Reports of
receptor tyrosine kinase (RTK) expression in
chordoma suggest that these
tumors may respond to
kinase inhibitor
therapy. Currently, there are no effective chemotherapeutic protocols for
chordoma. A tissue microarray containing 74
tumor specimens from primary
chordoma patients and 71 from their recurrent
tumors for a total of 145
tumor specimens was immunohistochemically analyzed for expression of a number of
proteins involved in signal transduction from RTKs.
Platelet-derived growth factor receptor-α (PDGFR-α),
epidermal growth factor receptor (EGFR), c-Met, and CD-34 were detected in 100, 92, 100, and 59% of cases, respectively. PDGFR-α and c-Met staining was of moderate to strong intensity in all cases. In contrast, total EGFR staining was variable; weak staining was detected in 10 cases. Our results contribute to the understanding of the expression of RTKs in skull base
chordomas and support the development of targeted
therapies that inhibit RTKs, which may have a synergistic effect for
chemotherapy in patients. There were statistically significant correlations between the expression of PDGFR-α, c-Met, and EGFR and disease-free survival. The results nonetheless suggest that
chordomas may respond to RTK inhibitors or modulators of other downstream signaling.