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Differential expression of epidermal growth factor receptor, c-Met, and HER2/neu in chordoma compared with 17 other
Paul M Weinberger1, Ziwei Yu, Diane Kowalski
1Section of Otolaryngology, Yale University, New Haven, CT 06520-8041, USA.
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.
Insights
Chordomas strongly express epidermal growth factor receptor (EGFR) and c-Met, suggesting potential therapeutic targets. HER2/neu expression was variable, but EGFR and c-Met showed a significant correlation in these rare bone tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Chordomas are rare malignant bone tumors.
- Understanding molecular targets is crucial for developing novel therapies.
- Expression profiling of key receptors can guide treatment strategies.
Purpose of the Study:
- To investigate the expression of c-Met, HER2/neu, and epidermal growth factor receptor (EGFR) in chordomas.
- To assess the potential of these targets for molecularly targeted therapies.
- To correlate the expression of these receptors within chordoma tissues.
Main Methods:
- Immunohistochemical analysis of archival chordoma tissue microarrays.
- Analysis of 12 chordoma samples and comparison with 51 other solid tumor types.
- Spearman rank correlation test to evaluate expression relationships.
Main Results:
- Strong expression of EGFR and c-Met was observed in most chordomas.
- Variable expression levels of HER2/neu were detected.
- A significant positive correlation was found between EGFR and c-Met expression (P = .006), particularly in primary chordomas.
Conclusions:
- Chordomas express HER2/neu, EGFR, and c-Met, similar to other solid tumors.
- The high expression of EGFR and c-Met suggests their potential as therapeutic targets.
- EGFR inhibitors, already in clinical use, may offer a viable treatment option for refractory chordomas, warranting further investigation.
