Activation of the EGFR/ERK pathway in high-grade mucoepidermoid carcinomas of the salivary glands

作者：Lujan B; Hakim S; Moyano S; Nadal A; Caballero M; Diaz A; Valera A; Carrera M; Cardesa A; Alos L^*

来源：British Journal of Cancer, 2010, 103(4): 510-516.

DOI：10.1038/sj.bjc.6605788

• mucoepidermoid carcinoma
• salivary gland carcinoma
• epidermal growth factor
• EGFR
• extracellular signal-regulated kinase
• ERK1/2

BACKGROUND: Mucoepidermoid carcinoma (MEC) shows differences in biological behaviour depending mainly on its histological grade. High-grade tumours usually have an aggressive biological course and they require additional oncological treatment after surgery.
METHODS: In a series of 43 MECs of the salivary glands, we studied the epidermal growth factor receptor (EGFR) gene by using dual-colour chromogenic in situ hybridisation (CISH). Moreover, we assessed the protein expressions of the EGFR and the activated extracellular signal-regulated kinases (pERK1/2) by using immunohistochemistry. These results were correlated with the histological grade of the tumours and the outcome of the patients.
RESULTS: The CISH study demonstrated a high-EGFR gene copy number, with balanced chromosome 7 polysomy, in 8 out of 11 high-grade MECs (72.7%), whereas 27 low-grade and 15 intermediate-grade tumours had a normal EGFR gene copy number (P<0.001). The EGFR gene gains correlated with disease-free interval (P=0.003) and overall survival of the patients (P=0.019). The EGFR protein expression had a significant correlation with the histological grade of the tumours but not with the outcome of the patients. The pERK1/2 expression correlated with histological grade of tumours (P<0.001), disease-free interval (P=0.004) and overall survival (P=0.001).
CONCLUSIONS: The EGFR/ERK pathway is activated in high-grade MECs with aggressive behaviour. Patients with these tumours who require oncological treatment in addition to surgery could benefit from EGFR and mitogen-activated protein kinase pathway inhibitors. British Journal of Cancer (2010) 103, 510-516. doi:10.1038/sj.bjc.6605788 www.bjcancer.

• 出版日期2010-8-10