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Published on: February 28, 2019
Receptor tyrosine kinases in sinonasal undifferentiated carcinomas--evaluation for EGFR, c-KIT, and HER2/neu
Rebecca D Chernock1, Arie Perry, John D Pfeifer
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Background:
Our objective was to identify the expression of epidermal growth factor receptor (EGFR), c-KIT (CD117), and HER2/neu in sinonasal undifferentiated carcinoma (SNUC).
Methods:
Immunohistochemistry for c-KIT (CD117), EGFR, and HER2/neu was performed on paraffin-embedded tissue from SNUC cases. A search for activating mutations in c-kit exons 9, 11, 13, and 17 or gene amplification was undertaken by high-resolution DNA melting curve analysis and fluorescence in situ hybridization (FISH) for c-kit and chromosome 4, respectively.
Results:
By immunohistochemistry, 9 of 11 cases (81.8%) were diffusely (4+) positive for c-KIT, 3 of 11 cases (27.3%) were positive for EGFR, and none of the cases were positive for HER2/neu. Neither activating mutations nor gene amplification of c-kit were detected in any of the 8 assessable tumors.
Conclusion:
c-KIT is frequently expressed in SNUC. However, the overexpression is not due to activating mutations or gene amplification.
Insights
c-KIT is commonly expressed in sinonasal undifferentiated carcinoma (SNUC), but this overexpression is not caused by mutations or gene amplification. Further research into SNUC biomarkers is needed.
Area of Science:
- Oncology
- Pathology
- Molecular Biology
Background:
- Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive malignancy.
- Understanding the molecular profile of SNUC is crucial for targeted therapy development.
Purpose of the Study:
- To investigate the expression of epidermal growth factor receptor (EGFR), c-KIT (CD117), and HER2/neu in SNUC.
- To determine if c-KIT overexpression in SNUC is associated with activating mutations or gene amplification.
Main Methods:
- Immunohistochemistry was used to assess the expression of EGFR, c-KIT, and HER2/neu in SNUC tissue samples.
- High-resolution DNA melting curve analysis and fluorescence in situ hybridization (FISH) were employed to detect c-KIT mutations and gene amplification.
Main Results:
- c-KIT was expressed in 81.8% of SNUC cases examined.
- EGFR was detected in 27.3% of cases, while HER2/neu was not found.
- No activating mutations or gene amplification of c-KIT were identified in the assessable tumors.
Conclusions:
- c-KIT is frequently expressed in SNUC, suggesting its potential role in the tumor's biology.
- The overexpression of c-KIT in SNUC is not driven by activating mutations or gene amplification.
- These findings highlight the need for further investigation into the mechanisms of c-KIT expression in SNUC.
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