Rare occurrence of EGFRvIII deletion in head and neck squamous cell carcinoma
Section snippets
Background
The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor and one of the most commonly affected growth factor receptors in cancer [1], [2]. EGFR is overexpressed in several epithelial cancers, including squamous cell carcinoma of the head and neck (HNSCC) in which it exhibits overexpression in up to 90% of tumors [2], [3], [4], [5]. Elevated levels of EGFR are usually induced by amplification of the EGFR gene or through altered transcriptional regulation and
Nucleic acid extraction from HNSCC samples
A total of 108 advanced HNSCC specimens were selected for the qRT-PCR analysis. Of these 108 samples, 56 were formalin fixed and paraffin embedded (FFPE) and 52 were Optimal Cutting Temperature compound (OCT) frozen. Samples were obtained from the Head and Neck Cancer tissue bank of the University of Chicago (IRB approved protocol UCCCC#8980). The clinical details of OCT frozen samples is given in Table 1. The FFPE samples were de-identified and their details are not available to us. A section
Results
In the present study we analyzed the presence of EGFRvIII in 638 HNSCC samples using rigorous gold-standard methodologies. qRT-PCR was used for 108 HNSCC samples. Around half of the samples were fresh frozen (52 samples) whereas the other half was FFPE (56 samples). In all these samples including the positive control we could successfully amplify the wild-type EGFR as well as GAPDH. However, none of the samples showed amplification of EGFRvIII when they were analyzed following methodology of
Discussion
The epidermal growth factor receptor (EGFR) is a growth-promoting molecule and it has long been associated with increased tumorogenesis [1]. EGFRvIII was first detected in glioblastoma [23] and was later reported to exist in other cancer types of epithelial origin [6], [7], [8], [9]; however, its presence in HNSCC remains controversial.
EGFRvIII in HNSCC was first described by Sok et al. (2006) [10], who found it in 42% of HNSCC tumors. EGFRvIII always appeared in conjunction with the wild-type
Conclusion
Our results establish that EGFRvIII expression is exceedingly rare in HNSCC as only 2 samples out of 638 (0.31%) samples or 2 samples out of 540 (0.37%) samples using mRNA based approaches were positive. We propose not to include EGFRvIII in regular diagnostic tests for the HNSCC given its’ rarity, and indeterminate biologic meaning for HNSCC.
Conflict of interest statement
None declared.
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2020, Oral OncologyCitation Excerpt :A modest increase in EGFR copy number was found to be a common event in SCCHN, and 11% of SCCHN cases exhibit high-level amplification of the EGFR gene. The EGFR variant III is present in an extremely low (less than 1%) frequency [12,28]. Taking focal amplifications and somatic mutations together, 17% of HNSCC cases exhibit genetic changes of EGFR and activation of downstream pathways [12,29].
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2015, Critical Reviews in Oncology/HematologyCitation Excerpt :Of note, EGFRvIII, a truncated EGFR variant, of presumed relevance in HNSCC [56], has been found associated with PI3K pathway activation [5,6]. However, recent data add to the controversy and rather suggest that EGFRvIII is not relevant in HNSCC [7]. Although most lung and head and neck carcinomas share exposure to tobacco, their activating mutations differ, underlining the tissue-specific nature of malignancies despite exposure to similar carcinogens [8].
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2015, Oral OncologyCitation Excerpt :It has been reported that mutation EGFRvIII was found in over 42% of 33 HNSCC tumors in conjunction with wild-type EGFR [84]. In contrast, another study conducted with 638 HNSCC samples showed that mutation is very rare in HNSCC, as only 2 samples (0.31%) were positive for EGFRvIII [85]. Many EGFR mutations have been related to HNSCC [86–92] (Fig. 2B).