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. 2010 Dec;28(10):1054-62.
doi: 10.3109/07357907.2010.512602. Epub 2010 Sep 27.

Combination of phosphorylated and truncated EGFR correlates with higher tumor and nodal stage in head and neck cancer

James Keller  1 , Kenneth R Shroyer, Shishir K Batajoo, Hong-Ling Zhao, Li Ming Dong, Michael J Hayman, Edward L Chan
Affiliations

Combination of phosphorylated and truncated EGFR correlates with higher tumor and nodal stage in head and neck cancer

James Keller et al. Cancer Invest. 2010 Dec.

Abstract

Epidermal growth factor receptor (EGFR) is a target in head and neck cancer. High EGFR expression and phosphorylated EGFR predicts poor survival in head and neck cancer patients, but does not correlate with advanced stage disease. The aim of this study is to determine if clinical biological correlates are more accurate when different aspects of EGFR are evaluated in combination. We analyzed the EGFR phosphorylation, expression, and mutations in 60 primary head and neck tumors. We not only found that head and neck tumors with either truncated or activated EGFR tend to have higher tumor and nodal stage but also discovered two novel EGFR truncations.

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Figures

Figure 1
Figure 1
Protein analysis by IPW and IHC. (a) Representative EGFR IPW analysis of HNSCC with their matched adjacent noncancerous tissues. EGF-stimulated COS cells are positive controls. (b) Comparison of EGFR expression between pEGFR+ (n = 22) and pEGFR− (n = 34) HNSCC. EGFR expression is calculated on a logarithmic scale. Tumors with log (EGFR expression) <4 are never phosphorylated; tumors with log (EGFR expression) between 4 and 8 are variable in their receptor activity level. (c) Comparison of processing time between pEGFR+ and pEGFR− tumors. The circle represents the mean. The error bars show 95% confidence interval of the means. (d) EGFR immunohistochemistry of a representative HNSCC, D2232# (100X). Viable tumor comprised about 50% of the tissue section. Noted immunohistochemical staining is detected in tumor epithelial cells, with minimal expression in tumor stroma. (e) pEGFR immunohistochemistry of a representative HNSCC, 106169# (200X). The black arrow points to the center of a focal area with no staining, while the light blue arrow points to the center of an area with membraneous staining. Note that the pEGFR IHC stain tends to be membraneous, more focal, and less intense than the EGFR IHC.
Figure 2
Figure 2
RNA analysis by RT-PCR. (a) RT-PCR screening of EGFR variants in a representative panel of primary HNSCC. FL-EGFR: full length EGFR. (b) DNA sequences of the exon 1–8 RT-PCR end products from three representative HNSCC. Top panel is DNA sequence representing EGFRvIII; middle panel shows EGFRΔ471 sequence; and the bottom panel is EGFRΔ660 sequence. All EGFR truncations were confirmed in both directions. (c) DNA sequences of the exon 17–22 RT-PCR end products from four representative HNSCC. The black arrow points to the missense mutation (C → T) in nucleotide 2197 of EGFR exon 19 of HNSCC106200#. The change in amino acid of this P733S mutation is illustrated by the amino acid sequence at the bottom. DNA sequences of the remaining three HNSCC (106176#, 107003#, and 106169#) are wild type. EGFR kinase mutations were confirmed in both directions. (d) RT-PCR screening of EGFR variants in five HNSCC cell lines. HNSCC106217# is the known positive control that expresses all three EGFR truncation mutants (see panel A).
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