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

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 diseasefree
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.