Research Letter |

EGFRvIII Expression in Squamous Cell Carcinoma of the Skin

Piotr J. Dziunycz, MD1; Zelmira Lazarova, MD2; Nathan Duncan, BS2; Stuart Wong, MD3; Marcy Neuburg, MD2; Günther F. L. Hofbauer, MD1; Edit B. Olasz, MD, PhD2
[+] Author Affiliations
1Department of Dermatology, University Hospital Zurich, Switzerland
2Department of Dermatology, Medical College of Wisconsin, Milwaukee
3Department of Oncology, Medical College of Wisconsin, Milwaukee
JAMA Dermatol. 2013;149(10):1240-1242. doi:10.1001/jamadermatol.2013.5230.
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Cutaneous squamous cell carcinoma (SCC) is a common cancer with an estimated 200 000 new cases annually.1 It is usually readily curable. However, a small subset of SCC tumors (approximately 10%, or 20 000 cases annually), termed “high-risk SCC,” carries an elevated risk of metastasis and death and accounts for nearly all the mortality associated with SCC.2 Epidermal growth factor receptor (EGFR) is overexpressed in a large percentage of SCC. Several therapeutic trials using EGFR blockade (with agents such as lapatinib, erlotinib, or panitumumab) to treat high-risk or metastatic SCCs are ongoing.3 Cetuximab, a chimeric IgG1 monoclonal antibody against EGFR, has been considered and used in the treatment of SCC; however, formal trials have not been performed, and good data are lacking.4 The most common form of mutant EGFR, called EGFRvIII, has been described in several cancers, including head and neck cancer. It has been shown that EGFRvIII contributes to enhanced growth of SCC and resistance to EGFR inhibitor drugs.5The aim of this study was the assessment of wild-type EGFR (wtEGFR) and EGFRvIII expression in skin SCC and its correlation with tumor biology.

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Figure 1.
Representative Immunohistochemical Staining of SCC Tumor Samples

Paraffin-embedded tumor samples were stained with mouse anti-epidermal growth factor receptor (EGFR) (31G7) antibodies, which recognize the wild-type EGFR (wtEGFR). Mouse monoclonal IgG1 was used as an isotype control. Immunoreactivity was rated as (A) 1 for weakly positive (<25% of the tumor mass stained), (B) 2 for moderately positive (25%-75% of the tumor mass stained), and (C) 3 for strongly positive (>75% of the tumor mass stained) staining. D, EGFR immunostaining scores of normal skin, in situ, and invasive squamous cell carcinoma (SCC). E, No significant differences in the expression of wtEGFR have been detected when comparing normal skin with SCC or when comparing well, moderately (mod), and poorly differentiated (diff) SCC. Error bars in D and E indicate standard deviations.

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Figure 2.
Representative Immunohistochemical Staining of Cutaneous SCC and SCC Metastasis

Representative Immunohistochemical staining of cutaneous squamous cell carcinoma (SCC) (A-C), and SCC metastasis for type III EGFR deletion mutant (EGFRvIII) and wild-type EGFR (D-F). (EGFR indicates epidermal growth factor receptor.) Metastatic SCCs were collected (n = 6 from 4 patients), paraffin embedded, and stained with hematoxylin-eosin (D), mouse anti-EGFR (31G7) (E), and mouse anti-EGFRvIII (L8A4) antibodies (F). Mouse monoclonal IgG1 was used as isotype control. None of the specimens studied expressed EGFRvIII. NR6M cells transduced with EGFRvIII served as a positive control.

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