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Updated: Jul 2, 2026
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Expression and mutation analysis of epidermal growth factor receptor in head and neck squamous cell carcinoma
Mahmoud A L Sheikh Ali1, Mehmet Gunduz, Hitoshi Nagatsuka
1Department of Oral Pathology and Medicine. Okayama University, Shikatacho 2-5-1, Okayama, Japan.
Abstract:
The epidermal growth factor receptor (EGFR)-RAS-RAF-mitogen-activated protein kinase signaling cascade is an important pathway in cancer development and recent reports show that EGFR and its downstream signaling molecules are mutated in a number of cancers. We have analyzed 91 Japanese head and neck squamous cell carcinomas (HNSCC) and 12 HNSCC cell lines for mutations in EGFR, ErbB2, and K-ras. Exons encoding the hot-spot regions in the tyrosine kinase domain of both EGFR (exons 18, 19, and 21) and ErbB2 (exons 18-23), as well as exons 1 and 2 of K-ras were amplified by polymerase chain reaction and sequenced directly. EGFR expression was also analyzed in 65 HNSCC patients using immunohistochemistry. Only one silent mutation, C836T, was found in exon 21 of EGFR in the UT-SCC-16A cell line and its corresponding metastasic cell line UT-SCC-16B. No other mutation was found in EGFR, ErbB2, or K-ras. All tumors showed EGFR expression. In 21 (32%) tumors, EGFR was expressed weakly (+1). In 27 (42%) tumors it was expressed (+2) moderately, and in 17 (26%) tumors high expression (+3) was detected. Overexpression (+2, +3) was found in 44 tumors (68%). A worse tumor differentiation and a positive nodal stage were significantly associated with EGFR overexpression (P = 0.02, P = 0.032, respectively). Similar to patients from western ethnicity, mutations are absent or rare in Japanese HNSCC. Protein overexpression rather than mutation might be responsible for activation of the EGFR pathway in HNSCC.
Insights
Mutations in EGFR, ErbB2, and K-ras are rare in Japanese head and neck squamous cell carcinomas (HNSCC). Instead, epidermal growth factor receptor (EGFR) protein overexpression is common and linked to worse tumor differentiation and nodal stage in HNSCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The epidermal growth factor receptor (EGFR) signaling pathway is crucial in cancer development.
- Mutations in EGFR and its downstream signaling molecules are implicated in various cancers.
- Understanding genetic alterations in Japanese head and neck squamous cell carcinomas (HNSCC) is important for targeted therapies.
Purpose of the Study:
- To investigate the frequency of mutations in EGFR, ErbB2, and K-ras in Japanese HNSCC.
- To analyze the expression levels of EGFR in HNSCC tumors.
- To determine the correlation between EGFR expression and clinicopathological features in HNSCC.
Main Methods:
- Analysis of mutations in hot-spot regions of EGFR (exons 18-21), ErbB2 (exons 18-23), and K-ras (exons 1-2) using polymerase chain reaction and direct sequencing.
- Immunohistochemical analysis of EGFR expression in 65 HNSCC tumors.
- Statistical analysis to correlate EGFR expression with tumor differentiation and nodal stage.
Main Results:
- Only one silent mutation (C836T) in EGFR exon 21 was detected in a cell line, with no other mutations found in EGFR, ErbB2, or K-ras.
- EGFR expression was observed in all HNSCC tumors, with 68% showing overexpression (+2 or +3).
- EGFR overexpression was significantly associated with worse tumor differentiation (P=0.02) and positive nodal stage (P=0.032).
Conclusions:
- Mutations in EGFR, ErbB2, and K-ras are infrequent in Japanese HNSCC.
- EGFR protein overexpression, rather than mutation, is likely responsible for pathway activation in HNSCC.
- EGFR overexpression serves as a potential biomarker for advanced disease and poorer prognosis in HNSCC.
