Gene amplification and protein overexpression of EGFR and ERBB2 in sinonasal squamous cell carcinoma

Abstract

Background: Sinonasal squamous cell carcinomas (SNSCC) are rare tumors with no etiological link to tobacco and alcohol, as opposed to other squamous cell carcinomas of the head and neck. Despite improvements in the field of surgery and radiotherapy, patients with these tumors still face a very unfavorable prognosis, partly due to its localization in a complex anatomical area, which is of special relevance for surgery and postoperative treatment. Therefore, there is a need for new therapeutic possibilities for this tumor type. Methods: Gene copy numbers of epidermal growth factor receptor (EGFR) and erythroblastic leukemia viral oncogene homolog 2 (ERBB2) were analyzed by FISH and MLPA and protein expression was evaluated by immunohistochemistry in 54 specimens SNSCC and the results were correlated with clinico-pathological and follow-up data. Results: EGFR gene copy number increase were observed in 20/45 (44%) cases, and 21/54 (39%) tumors showed EGFR protein overexpression. Eight of 38 tumors (21%) showed ERBB2 copy number increase, and 4/54 (7%) exhibited elevated protein expression levels. Both copy number increase and protein overexpression of EGFR and ERBB2 were mutually exclusive. KRAS mutations were absent in 37 cases analyzed. Conclusion: A substancial proportion of SNSCC carry alterations in EGFR or ERBB2. Together with the absence of KRAS mutations, these findings indicate that therapies targeting these molecules could be a promising addition to the therapeutical options for these tumors.