Evaluation of EGFR as a prognostic and diagnostic marker for head and neck squamous cell carcinoma patients

Abstract

Approximately 90% of all head and neck tumors are squamous cell carcinomas. The overall survival of patients with head and neck squamous cell carcinoma (HNSCC) is low (≤50%). A non-invasive marker of disease progression is sorely required. The present study focused on the plasmatic levels of epidermal growth factor receptor (EGFR) in HNSCC patients (N=92) compared with healthy (N=29) and diabetic [type 2 diabetes mellitus (T2DM); N=26] controls. Enzyme-linked immunosorbent assay using antibodies against the extracellular region of EGFR (L25-S645) was performed. No significant changes were observed between diabetic and healthy controls. However, there were significantly higher EGFR plasma levels in HNSCC patients compared with both control groups (P=0.001 and 0.005, respectively). Receiver operating characteristic curve analysis identified a sensitivity of 76.09%, a specificity of 67.27% and an area under curve of 0.727 for this comparison. No significant association was observed between EGFR plasma levels and tumor stage, tumor grade, lymph node or distant metastasis occurrence, smoking habit or hypertension. However, the presence of human papillomavirus infection and T2DM in HNSCC patients had borderline effect on the plasma EGFR levels. Survival analysis revealed no significant influence of plasmatic EGFR levels on the overall and disease-specific survival of HNSCC patients. In conclusion, EGFR plasma levels appear to be a relatively promising diagnostic, but poor prognostic, HNSCC marker.

Keywords: EGFR; biomarker; diagnosis; head and neck tumors; plasma; spinocellular cancer.

Figure 1.

Schematic representation of EGFR protein (170-kDa). EGFR is composed of an extracellular highly glycosylated ligand-binding domain (comprising amino acids 1–621; exons 1–15), a hydrophobic transmembrane domain (amino acids 622–644; exons 15–17) and an intracellular domain with tyrosine kinase activity for signal transduction (amino acids 645–1,186; exons 18–28). I–IV denote subdomains of the extracellular domain. The figure was adapted from Albitar et al (1). TMD, transmembrane domain; TK, tyrosine kinase; EGFR, epidermal growth factor receptor.

Figure 2.

Plasmatic EGFR levels. (A) Plasma EGFR levels in head and neck squamous cell carcinoma patients and in two control groups (*P<0.05 vs. controls). (B) Receiver operating characteristic curve analysis indicating the sensitivity and specificity of plasma EGFR detection. (C) Plasma EGFR levels in human papillomavirus-positive and -negative patients. (D) Plasma EGFR levels and type 2 diabetes mellitus status in patients. EGFR, epidermal growth factor receptor; T2DM, type 2 diabetes mellitus; HPV, human papillomavirus.

Figure 3.

Survival analysis. (A) Kaplan-Meier overall survival analysis. (B) Disease-specific survival analysis. High/low EGFR indicate EGFR values above/below the mean EGFR values. P-value was calculated by Cox proportional hazard regression analysis. EGFR, epidermal growth factor receptor.