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Expression of epidermal growth factor receptor, ERBB2 and KIT in adult soft tissue sarcomas: a clinicopathologic
Osamu Sato1, Takuro Wada, Akira Kawai
1Department of Orthopaedic Surgery, Sapporo Medical University, Sapporo, Japan.
Background:
Little is known about the expression of receptor tyrosine kinases in adult soft tissue sarcomas (STS). In the current study, the authors analyzed the expression of epidermal growth factor receptor (EGFR), ERBB2, and KIT in 281 patients with STS who were treated in a single institution. Verification of the presence of an association with prognosis was performed.
Methods:
The current study included 281 adult patients with STS of the extremity and trunk who were diagnosed and treated in the National Cancer Center, Tokyo. Expression was assessed using immunohistochemical stains for EGFR, ERBB2, and KIT on formalin-fixed, paraffin-embedded tissue sections by standard avidin-biotin peroxidase complex technique and EGFR detection system.
Results:
Positive staining of EGFR was observed in 168 of 281 (60%) patients. Positive staining was common in pleomorphic malignant fibrous histiocytomas (89%), myxofibrosarcomas (89%), synovial sarcomas (76%), malignant peripheral nerve sheath tumors (89%), and leiomyosarcomas (73%). It was less common in well differentiated liposarcomas (38%), fibrosarcomas (36%), and myxoid liposarcomas (6%). In contrast, positive staining of ERBB2 and KIT was very limited. Increased levels of EGFR were significantly associated with a decreased probability of overall survival (P = 0.01), although by univariate analysis; probability of overall survival at 5 years was 64% in patients with increased levels of EGFR and 79% in patients without such overexpression. The overexpression of EGFR was significantly associated with histologic grade (P < 0.001). Moreover, stratified log-rank test revealed that there is an interrelation between EGFR overexpression and histologic grade.
Conclusions:
EGFR overexpression was found to be a negative prognostic factor of adult STS, which is strongly associated with histologic grade. STS patients with EGFR overexpression may benefit from treatment with currently available biospecific inhibitors for EGFR.
Insights
Epidermal growth factor receptor (EGFR) overexpression is a negative prognostic factor in adult soft tissue sarcomas (STS), linked to higher histologic grade. Patients with EGFR overexpression may benefit from targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Receptor tyrosine kinase expression in adult soft tissue sarcomas (STS) is poorly understood.
- This study investigates the expression of epidermal growth factor receptor (EGFR), ERBB2, and KIT in adult STS.
Purpose of the Study:
- To analyze the expression of EGFR, ERBB2, and KIT in adult STS.
- To determine the association between the expression of these receptors and patient prognosis.
Main Methods:
- Immunohistochemical analysis of EGFR, ERBB2, and KIT expression in 281 adult STS tissue samples.
- Correlation of receptor expression with histologic grade and patient survival data.
Main Results:
- EGFR overexpression was detected in 60% of patients and was common in several STS subtypes.
- EGFR overexpression was significantly associated with a worse overall survival and higher histologic grade.
- ERBB2 and KIT expression was very limited in the studied cohort.
Conclusions:
- EGFR overexpression serves as a negative prognostic indicator in adult STS.
- EGFR overexpression is strongly linked to the histologic grade of STS.
- Adult STS patients with EGFR overexpression might respond favorably to EGFR-targeted therapies.
