Epidermal growth factor receptor kinase domain mutations are rare in salivary gland carcinomas

Abstract

Activating mutations within the epidermal growth factor (EGFR) tyrosine kinase domain identify non-small cell lung cancer patients with improved clinical response to tyrosine kinase inhibitor therapy. Recently, we identified two EGFR mutations in a cohort of 25 salivary gland carcinomas (SGCs) by screening the tumour samples for the both most common hotspot mutations in exons 19 and 21 by allele-specific PCR. Here, we present a comprehensive sequencing analysis of the entire critical EGFR tyrosine kinase domain in 65 SGC of the main histopathological types. We found EGFR mutations in the tyrosine kinase domain to be a rare event in SGCs. No additional mutations other than the two known exon 19 deletions (c.2235_2249del15) in a mucoepidermoid carcinoma and an adenoid cystic carcinoma have been detected. Other putative predictive markers for EGFR-targeted therapy in SGCs might be relevant and should be investigated.

EGFR L861Q mutation is a frequent feature of pulmonary mucoepidermoid carcinoma

“…There was also no case with EGFR genetic alterations among Wve PMEC in Rossi's data (Rossi et al 2009). Dahse et al found EGFR mutations in the tyrosine kinase domain to be a rare case in salivary MEC (Dahse et al 2009). …”

A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC

“…Nevertheless, the low frequency of HER2 overexpression in ACC [34,35] has hampered further investigation of HER2 targeting agents and resulted in the early closure of a phase II study evaluating trastuzumab after enrollment of only two ACC patients [29]. EGFR expression by IHC is present in approximately 75%-85% of ACC [36,37]. Phase II trials of EGFR inhibitors in patients with unknown EGFR status have demonstrated no objective responses [27,28].…”

Adenoid Cystic Carcinoma of the Lung with an <i>EGFR</i> Mutation

“…In one study, based on screening for salivary gland carcinoma, two drug-sensitizing EGFR exon 19 deletion mutations (E746-A750 deletion) were identified in a case of adenoid cystic carcinoma and Intern Med 55: 1621-1624, 2016 DOI: 10.2169/internalmedicine.55.6592 mucoepidermoid carcinoma of the parotid gland. The authors found that one of 11 patients had EGFR mutations (13). In contrast, Macarenco and colleagues demonstrated that none of the 12 patients in their series had EGFR mutations in cases of adenoid cystic carcinoma (14).…”