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Epidermal growth factor receptor in osteosarcoma: expression and mutational analysis
Yong Hannah Wen1, Hartmut Koeppen, Roberto Garcia
1Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Abstract:
Activation of intracellular mitogenic signal transduction pathways driven by the ErbB family of receptor tyrosine kinases has been implicated in the development and/or progression of a variety of cancers. Studies on ErbB receptors in osteosarcoma have focused on HER-2 and have produced conflicting results with few studies evaluating the expression of the epidermal growth factor receptor (EGFR). In this study, we determined the level of expression of EGFR and the mutational status of the EGFR receptor in a subset of osteosarcoma tumor samples as well as in a series of established bone tumor-derived cell lines. EGFR protein expression was detected in the form of strong membranous staining by immunohistochemistry in 21 (57%) of 37 cases analyzed. Six of 12 (50%) osteosarcoma cell lines revealed moderate to high expression levels of EGFR. Two somatic alterations (E829E and R831C) were identified in the cytoplasmic domain of the EGFR gene in 1 of 10 tumor samples. The significance of these findings for the pathobiology of osteosarcomas will be investigated further.
Insights
Epidermal growth factor receptor (EGFR) is expressed in over half of osteosarcoma cases and cell lines. Researchers identified two new EGFR gene alterations in tumor samples, warranting further investigation into their role in osteosarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- ErbB receptor tyrosine kinases, including EGFR, are implicated in various cancers.
- Osteosarcoma research has primarily focused on HER-2, with conflicting results and limited evaluation of EGFR expression.
Purpose of the Study:
- To determine the expression level of EGFR in osteosarcoma.
- To analyze the mutational status of the EGFR gene in osteosarcoma samples and cell lines.
Main Methods:
- Immunohistochemistry was used to detect EGFR protein expression in 37 osteosarcoma tumor samples.
- EGFR expression was assessed in 12 established bone tumor-derived cell lines.
- Somatic alterations in the EGFR gene were identified using sequencing.
Main Results:
- EGFR protein expression was observed in 57% (21 of 37) of osteosarcoma cases, showing strong membranous staining.
- Moderate to high EGFR expression was found in 50% (6 of 12) of osteosarcoma cell lines.
- Two somatic alterations (E829E and R831C) were detected in the EGFR gene's cytoplasmic domain in one tumor sample.
Conclusions:
- EGFR is frequently expressed in osteosarcoma, suggesting a potential role in the cancer's development or progression.
- The identified EGFR alterations may have implications for osteosarcoma pathobiology.
- Further research is needed to elucidate the functional significance of EGFR expression and mutations in osteosarcoma.
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