Expression and Clinical Significance of Epidermal Growth Factor Receptor and Type 1 Insulin-Like Growth Factor Receptor in Nasopharyngeal Carcinoma

Abstract

Objectives: Epidermal growth factor (EGF) and type 1 insulin-like growth factor (IGF-1) receptors play an important role in the growth and apoptosis of nasopharyngeal carcinoma (NPC). They were separately found to be associated with prognosis in patients with NPC. To date, their expression correlation and clinicopathologic significance have never been specifically addressed in NPC.

Methods: Seventy-five patients with NPC and 21 noncancerous nasopharyngeal epithelial samples were accrued between 1998 and 2006 in a single hospital. The expressions of EGF and IGF-1 receptors were detected by immunohistochemical staining in the 75 NPC samples and the 21 noncancerous samples. Furthermore, the messenger RNA and protein expressions were assessed by real-time quantitative polymerase chain reaction and the Western blot technique, respectively, in NPC cell lines and normal nasopharyngeal epithelial cells.

Results: The 5-year survival rates, assessed by the Kaplan-Meier method, were 71.4% and 66.6% in the EGF and IGF-1 receptor protein-negative groups, respectively, whereas they were only 28.6% and 33.3% in the receptor protein-positive groups. The levels of these two proteins significantly correlated with each other, and the overexpression rates of EGF and IGF-1 receptors were 65.3% and 56% in nasopharyngeal samples, respectively. Furthermore, both protein expressions were significantly higher in NPC patients with cervical lymph node or distant metastasis than in NPC patients without lymph node or distant metastasis. Recurrence more often appears in cases positive for both proteins than in cases negative for both proteins. The expression levels of the receptor messenger RNA and proteins were higher in several NPC cell lines than in normal nasopharyngeal epithelial cells.

Conclusions: These findings demonstrate that both receptor proteins may play an important role in the invasion, metastasis, and recurrence of NPC. Both receptors are valuable markers for assessing the prognosis of NPC. Their expression at such high frequencies provides the basis of combined targeted therapy with specific pharmacologic inhibitors to enhance the effects of radiotherapy and chemotherapy.