EGFR overexpression is not common in patients with head and neck cancer. Cell lines are not representative for the clinical situation in this indication

Abstract

BackgroundBased on expression data, Epidermal Growth Factor Receptor (EGFR) emerged as therapeutic target in Head and Neck Cancer but clinical efficacy of EGFR inhibitors was very limited. We reinvestigated the EGFR expression and activation status necessary for response in cell lines and compared that to clinical samples.MethodsClinical samples of head and neck squamous cell carcinoma (HNSCC, n=63), mostly from late stage (IV) and poorly or undifferentiated character and cultured cell lines (n=14) were tested by immunohistochemistry (IHC) (n=55) and sandwich immunoassays (n=63) for expression and phosphorylation of EGFR (Tyrosine-1173). Response of 14 different HNSCC cell lines to Erlotinib was tested in proliferation assays.ResultsMost HNSCC cell lines respond to Erlotinib. EGFR is phosphorylated in these cell lines. Resistant cell lines display very low level EGFR expression and phosphorylation. EGFR activity in clinical samples is significantly below that observed in cell lines. In clinical samples, EGFR is not overexpressed on the single cellular level. We show similar levels of EGFR expression in growing keratinocytes and tumor cells.ConclusionsCell lines are not representative of the clinical situation in HNSCC. Larger studies should investigate whether patient subgroups with activating EGFR mutations or overexpression can be identified.

Circadian (De)regulation in Head and Neck Squamous Cell Carcinoma

“…Still, it seems that clinical outcomes with tyrosine kinase inhibitors Erlotinib and Gefitinib were not satisfactory so far. In addition, in combined regimens of the EGFR directed monoclonal antibody Cetuximab with chemo- or radiotherapy with a satisfactory result, no correlation of the therapeutic efficacy was observed with EGFR copy number, expression or mutations [23]. The cellular signaling pathways of the receptors Janus kinase (JAK) activators of the transcription factor STAT and phospholipase-Cy/protein kinase C, are also activated along with EGFR phosphorylation [24].…”

Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer: Her1–4 and c-Met in Conjunction with the Clinical Features and Human Papillomavirus (p16) Status

“…Of note, SOP for GFR analyses in HNSCCs are still missing. In addition, high ex-pression rates in 2D cell cultures were found to be not representative for 3D spherical tumor tissue [ 43 , 44 ]. Since high EGFR expression has not been found to influence cetuximab treatment, lower expression rates do not seem to be relevant [ 45 , 46 ].…”

Human Tumor–Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing

“…While many studies report EGFR overexpression in HNSCC, supporting data are inconsistent and limited due to the large variation in antibodies, the lack of controls, and testing only at the RNA level [24]. One study revealed that EGFR protein overexpression more commonly occurs in established HNSCC cell lines (n = 14) than in clinical samples (n = 55) [25]. Clinical HNSCC samples (n = 55) did not overexpress EGFR at the protein level compared to healthy mucosa (n = 46) [25].…”

“…One study revealed that EGFR protein overexpression more commonly occurs in established HNSCC cell lines (n = 14) than in clinical samples (n = 55) [25]. Clinical HNSCC samples (n = 55) did not overexpress EGFR at the protein level compared to healthy mucosa (n = 46) [25].…”