Role of EGFR as prognostic factor in head and neck cancer patients treated with surgery and postoperative radiotherapy: proposal of a new approach behind the EGFR overexpression

Abstract

In an era of personalized treatment, there is a great interest in identifying factors which might predict patient response to radiotherapy (RT). The role of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) remains still controversial. We performed a retrospective analysis on the prognostic value of EGFR in HNSCC patients treated with surgery and postoperative RT through a semiquantitative immunohistochemical analysis of EGFR membrane expression. We retrospectively analyzed 65 HNSCC patients treated in our Institute from 1997 to 2003 who underwent adjuvant RT after surgery. Median follow-up was 43.5 months (range 0.2-173 months). None of these patients were treated with postoperative concomitant chemotherapy. Tumor samples were obtained from surgical specimens. Membrane features (intensity, extension) of EGFR expression were evaluated, and a statistical analysis (univariate and multivariate) was conducted to correlate these parameters with overall survival (OS) and disease-free survival (DFS). Patients with an intense and complete labeling of EGFR presented worse OS and DFS compared with groups obtained by all other possible combination, and the difference was borderline statistically significant (P = 0.08 for OS and P = 0.006 for DFS). Moreover, a stratification of patients was performed considering EGFR expression on the tumor tissue and classifying its distribution as "homogeneous" or "heterogeneous." We found that patients showing an "heterogeneous" EGFR expression distribution had worse OS and DFS compared to the "homogeneous" group of patients. Based on our results, EGFR expression, especially referring to membrane features (semiquantitative analysis), might have a prognostic value for OS and DFS in locally advanced HNSCC treated with surgery and adjuvant RT. Prospective trials could be useful to confirm the prognostic role of EGFR expression and also to assess a predictive role to select that might benefit from more aggressive treatments.

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

“…In this rapidly evolving era of high‐throughput omics technology, thousands of candidate molecules can be investigated easily without an a priori hypothesis. A more specific, targeted approach is a post‐hoc, data‐driven investigational study design, rather than conventional pathway rationale‐driven or hypothesis‐driven designs . Setting a relevant, reproducible biomarker cutoff value to guide subsequent clinical measurement and validation can also be a difficult hurdle in biomarker test planning …”

“…A more specific, targeted approach is a posthoc, data-driven investigational study design, rather than conventional pathway rationale-driven or hypothesis-driven designs. 7 Setting a relevant, reproducible biomarker cutoff value to guide subsequent clinical measurement and validation can also be a difficult hurdle in biomarker test planning. 7 Furthermore, results of biomarker analyses can be notoriously inconsistent, making it difficult to draw robust conclusions.…”

“…7 Setting a relevant, reproducible biomarker cutoff value to guide subsequent clinical measurement and validation can also be a difficult hurdle in biomarker test planning. 7 Furthermore, results of biomarker analyses can be notoriously inconsistent, making it difficult to draw robust conclusions. 8 Some studies might show negative or discrepant results, while the same biomarker might clearly demonstrate positive associations in other studies-for example, CCND1, 9 cMET, 10 p16, [10][11][12] EGFR, 13 and ERCC1.…”

Developing Predictive or Prognostic Biomarkers for Charged Particle Radiotherapy

“…Interestingly, EGFR overexpression, common to HNSCC, as measured by immunohistochemistry (IHC), is a strong predictor of locoregional recurrence after either surgical radiotherapy or induction chemotherapy [3–6]. However, the role of EGFR expression as a biomarker remains controversial [7–9]. …”

Long noncoding RNA Lnc‑EGFR promotes cell proliferation and inhibits cell apoptosis via regulating the expression of EGFR in human tongue cancer

“…The epidermal growth factor receptor (EGFR) is a transmembrane protein, which is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands (11,12). Mutations that lead to EGFR overexpression or overactivity have been reported in multiple cancers, including squamous-cell carcinoma of lung (more than 80% cases) (13), anal cancers (14) and epithelial tumors of the head and neck (80-100% cases) (15). Particularly, EGFR played a prognostic role in the prognosis of tongue cancer (16).…”