Differential expression of epidermal growth factor receptor, c-Met, and HER2/neu in chordoma compared with 17 other malignancies

Objective: To examine the expression of c-Met, c-Erb-b2 (HER2/neu), and epidermal growth factor (EGFR) in a cohort of 12 chordomas, based on the current and future availability of targeted molecular inhibitors. Design: Protein expression levels were analyzed by immunohistochemical analysis from archival tissue using multitumored tissue microarray and by Spearman rank correlation test. Setting: Tertiary care facility. Subjects: We assembled the cohort of 12 chordomas from patients treated at the Yale-New Haven Hospital from 1986 to 2003 and compared them with 51 other tumors from 17 assorted solid tissue tumor types along with 1 sample of healthy tissue from each site. Main Outcome Measure: The expression of c-Met, HER2/neu, and EGFR. Results: Most chordomas displayed strong expression of EGFR and c-Met, whereas a variable level of expression of HER2/neu was seen. In addition, we noted a strong correlation between EGFR and c-Met expression, especially for primary chordomas (P=.006). Conclusions: Chordomas, like many other solid-tissue tumors, express HER2/neu, EGFR, and the hepatocyte growth factor/scatter factor receptor c-Met. Most chordomas had strong expression of both the hepatocyte growth factor/scatter factor receptor and EGFR. Inhibitors to EGFR are already in clinical use for other solid-tissue tumors and represent a potentially viable experimental treatment option for refractory chordoma. Further studies are required to investigate these findings.