Integrating Epidermal Growth Factor Receptor Assay With Clinical Parameters Improves Risk Classification for Relapse and Survival in Head-and-Neck Squamous Cell Carcinoma

Abstract

PURPOSE Epidermal growth factor receptor (EGFR) overexpression has been consistently found to be an independent predictor of local-regional relapse (LRR) after radiotherapy. We assessed the extent by which it can refine risk classification for overall survival (OS) and LRR in patients with head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS EGFR expression in locally advanced HNSCC was measured by immunohistochemistry (IHC) in a series of patients randomized to receive accelerated or conventional radiation regimens in a phase III trial. Subsequently, data of the two series were pooled (N=533) for conducting a recursive partitioning analysis that incorporated clinical parameters (performance status, primary site, T- and N-categories, etc.) and four molecular markers (EGFR, p53, Ki-67, and microvessel density). RESULTS This study confirmed that patients with higher than median levels of tumor EGFR expression had a lower OS (RR: 1.90, P=0.0010) and a higher LRR (RR: 1.91, P=0.0163). Of the four markers analyzed, only EGFR was found to contribute to refining classification of patients into three risk classes with distinct OS and LRR outcomes. The addition of EGFR to three clinical parameters could identify patients having up to a 5-fold difference in the risk of LRR. CONCLUSIONS Adding pretreatment EGFR expression data to known robust clinical prognostic variables improved the estimation of the probability for OS and LRR after radiotherapy. Its use for stratifying or selecting patients with defined tumor feature and pattern of relapse for enrollment into clinical trials testing specific therapeutic strategy warrants further investigation.

DecreasedSMAD4expression is associated with induction of epithelial-to-mesenchymal transition and cetuximab resistance in head and neck squamous cell carcinoma

“…It has long been understood that EGFR overexpression as determined by immunohistochemistry is associated with poor survival in HNSCC patients. [5][6][7][8] Furthermore, recent comprehensive genomic analyses of HNSCCs have confirmed that EGFR is altered by increased copy number and mutations. [9][10][11] Based on these data, EGFR-targeted agents have been developed and cetuximab, a monoclonal antibody directed against EGFR, is currently FDA-approved for use in HNSCC patients.…”

Resistance of oral squamous cell carcinoma cells to cetuximab is associated with EGFR insensitivity and enhanced stem cell-like potency

“…Variants of the genes encoding the EGFR family are oncogenes of various tumors. Upregulation of EGFR expression in many human epithelial cancers is associated with advanced tumor stage and an unfavorable prognosis (6,7). Thus, EGFR is considered to be not only a useful prognostic biomarker but also a promising therapeutic target, and specific anti-EGFR monoclonal antibodies (mAbs) to extracellular domains of the proteins, and tyrosine kinase inhibitors (TKIs), have been developed and used in cancer treatment.…”

Relationship between Epidermal Growth Factor Receptor Status, p16INK4A, and Outcome in Head and Neck Squamous Cell Carcinoma

“…A number of studies have investigated the relationship between high EGFR protein expression (as determined by IHC) and poor outcome in HNSCC. Results have been varied, with several groups showing correlations between EGFR protein levels and outcome (11,(16)(17)(18)(19)(20)(21) whereas other groups have shown no correlation (22,23). Increased EGFR gene copy number in HNSCC, as determined by FISH, was reported by Chung and colleagues (24), who showed that high EGFR gene copy number (as defined by high polysomy or amplification) was frequent in HNSCC and was a negative prognostic marker.…”