Oncotarget

Research Papers:

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

Sami Sebastian Khaznadar, Martin Khan, Elke Schmid, Sebastian Gebhart, Eva-Tessina Becker, Thomas Krahn and Oliver von Ahsen _

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Oncotarget. 2018; 9:28965-28975. https://doi.org/10.18632/oncotarget.25656

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Abstract

Sami Sebastian Khaznadar1,4,*, Martin Khan2,3,*, Elke Schmid1, Sebastian Gebhart2, Eva-Tessina Becker2, Thomas Krahn1 and Oliver von Ahsen1

1Biomarker Research, Bayer AG, 13353 Berlin, Germany

2Charite, Berlin, 13353 Berlin, Germany

3Present address: Klinikum Dahme-Spreewald GmbH, 15711 Königs-Wusterhausen, Germany

4Present address: University Bonn, 53113 Bonn, Germany

*These authors have contributed equally to this work

Correspondence to:

Oliver von Ahsen, email: oliver.vonahsen@bayer.com

Keywords: HNSCC; Erlotinib; IHC; MSD; tyrosine kinase inhibitor

Received: December 15, 2017    Accepted: May 31, 2018    Published: June 22, 2018

ABSTRACT

Background: Based 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.

Methods: Clinical 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.

Results: Most 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.

Conclusions: Cell 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.


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