Abstract 4661: Decreased epidermal growth factor receptor plasma levels as an indicator for head and neck squamous cell carcinoma case status and disease progression

Abstract

Abstract The epidermal growth factor receptor (EGFR), c-Met and G-protein-coupled receptor signaling pathways contribute to head and neck squamous cell carcinoma (HNSCC) growth. To assess these pathways in HNSCC patients, we measured plasma levels of EGFR, the EGFR ligands transforming growth factor alpha (TGF-α) and amphiregulin (AR), the c-Met ligand hepatocyte growth factor (HGF) and COX-2, a component of prostaglandin production, in HNSCC patients (n=22) and cancer-free controls (n=32) enrolled through an Early Detection Research Network- (EDRN-) sponsored effort. Analytes were measured using a multiplex enzyme-linked immunosorbent assay. Differences in analyte levels between cases and controls and the prognostic potential of each analyte were evaluated. EGFR plasma levels were significantly decreased (P=0.04, rank sum test (RST)) and HGF plasma levels significantly increased (P<0.01, RST) in HNSCC cases compared to cancer-free controls. TGF-α levels tended to be higher in HNSCC cases (P=0.07, RST) while AR and COX-2 levels did not differ between cases and controls (P=0.32 and 0.32, respectively RST). Area under the Receiver Operating Characteristic (ROC) curve for HGF levels in subjects with low EGFR plasma levels was 0.92. EGFR plasma levels were significantly reduced in HNSCC cases who were former or active smokers compared to never smokers (P = 0.009, Kruskal-Wallis test (KWT)), but no difference in EGFR plasma levels by smoking status was observed among cancer-free controls (P = 0.97, KWT). HGF plasma levels tended to be lower in HNSCC cases who were never smokers (P=0.06 KWT) but did not differ by smoking status among cancer-free controls (P=0.16, KWT). Low EGFR plasma levels were associated with significantly reduced progression-free survival (PFS) in EDRN HNSCC cases (P = 0.03, log rank test); no other analyte tested was associated with PFS. We noted a negative correlation between EGFR plasma levels in EDRN HNSCC cases and previously reported EGFR tumor levels assessed by immunohistochemical staining that was not significant (Spearman's rho=-0.41, P=0.10, n=17). Plasma EGFR and HGF levels may provide indications of HNSCC cancer status, and EGFR plasma levels may be a valuable prognostic indicator for patients with HNSCC. Decreased plasma EGFR levels in HNSCC patients were likely not due to general effects related to smoking and instead may reflect tissue characteristics specific to tobacco-related cancers. We found EGFR plasma levels in HNSCC patients were not positively correlated with EGFR tumor levels. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4661.