Epidermal Growth Factor Receptor Overexpression and Genetic Aberrations in Metastatic Squamous-Cell Carcinoma of the Skin

Abstract

Background: Cutaneous squamous-cell carcinoma (SCC) sometimes causes lymph node metastasis and results in poor prognosis. However, little is known about cytogenetic alterations underlying tumor progression or metastasis. The aim of the present study was to investigate the genetic aberrations and expression of epidermal growth factor receptor (EGFR) in metastatic SCC of the skin. Methods: We undertook comparative genomic hybridization (CGH) analysis of 4 specimens which were obtained from a case of cutaneous SCC, including the primary lesion and 3 lymph nodes of the metastatic lesion. Results: Only one amplified locus (7p12–13) was detected in any metastatic lymph node, in which the EGFR gene is located. Therefore, we applied immunohistochemistry for EGFR to 5 cases of metastatic SCC including the case analyzed using CGH and 4 other cases (5 primary and 5 metastatic lesions). EGFR was expressed in 4 of 5 cases (both primary and metastatic lesions, including the case analyzed using CGH), and the staining patterns of primary and metastatic lesions were different. The primary tumors were focally weakly positive for immunostaining (+), whereas the 4 metastases were diffusely and strongly positive (+++). Conclusions: Our findings suggest that the clone with EGFR expression might selectively metastasize in some cutaneous SCCs. The existence of an EGFR-negative case reveals that EGFR expression is not always required for skin carcinogenesis, but expression of EGFR might confer metastatic potential of cutaneous SCCs.

RasGRP1 Transgenic Mice Develop Cutaneous Squamous Cell Carcinomas in Response to Skin Wounding

“…1,5 This suggests that other mechanisms of Ras activation play a role in the human disease. For example, epidermal growth factor receptor overexpression by amplification is known to occur in human SCC, 6,7 and epidermal growth factor receptor could lead to the biochemical stimulation of Ras. In animal models, overexpression of epidermal growth factor receptor ligands like transforming growth factor-␣, 8 or a dominant form of the Ras exchange factor Sos of seven less (SOS), 9 act as an initiation event in the epidermis, further demonstrating that alterations in Ras upstream signals could lead to tumorigenesis in the skin via wildtype Ras activation.…”

Differential ErbB1 Signaling in Squamous Cell versus Basal Cell Carcinoma of the Skin

“…48 Relative expression of these receptors in tumor cells versus adjacent epidermis was not addressed in that study, which used bulk tumor specimens. In cutaneous SCC, studies have reported variable levels of ErbB1 and ErbB2 in primary tumors but increased expression of ErbB1 47 and ErbB2 46 proteins in metastatic lesions.…”

High-risk Cutaneous Squamous Cell Carcinoma

“…85 Targeted therapies and forms of immunotherapy utilize the overexpression of epidermal growth factor receptor (EGFR) in the setting of cSCC to disrupt cell proliferation. [86][87][88] These novel treatments, which include monoclonal antibodies, such as cetuximab, can offer an overall disease control rate of 69%, as seen in a phase II trial using cetuximab in the setting of metastatic cSCC. 88 A further stage III randomized trial adding cetuximab to cisplatin significantly improved treatment response when compared with placebo (26.3 vs 9.8%; p=0.29).…”