Analyzing expression and phosphorylation of the EGF receptor in HNSCC

TY - JOUR

T1 - Analyzing expression and phosphorylation of the EGF receptor in HNSCC

AU - Kriegs, Malte

AU - Clauditz, Till Sebastian

AU - Hoffer, Konstantin

AU - Bartels, Joanna

AU - Buhs, Sophia

AU - Gerull, Helwe

AU - Zech, Henrike Barbara

AU - Bußmann, Lara

AU - Struve, Nina

AU - Rieckmann, Thorsten

AU - Petersen, Cordula

AU - Betz, Christian Stephan

AU - Rothkamm, Kai

AU - Nollau, Peter

AU - Münscher, Adrian

PY - 2019/9/19

Y1 - 2019/9/19

N2 - Overexpression of the epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC) is considered to cause increased EGFR activity, which adds to tumorigenicity and therapy resistance. Since it is still unclear, whether EGFR expression is indeed associated with increased activity in HNSCC, we analyzed the relationship between EGFR expression and auto-phosphorylation as a surrogate marker for activity. We used a tissue micro array, fresh frozen HNSCC tumor and corresponding normal tissue samples and a large panel of HNSCC cell lines. While we observed substantial overexpression only in approximately 20% of HNSCC, we also observed strong discrepancies between EGFR protein expression and auto-phosphorylation in HNSCC cell lines as well as in tumor specimens using Western blot and SH2-profiling; for the majority of HNSCC EGFR expression therefore seems not to be correlated with EGFR auto-phosphorylation. Blocking of EGFR activity by cetuximab and erlotinib points to increased EGFR activity in samples with increased basal auto-phosphorylation. However, we could also identify cells with low basal phosphorylation but relevant EGFR activity. In summary, our data demonstrate that EGFR expression and activity are not well correlated. Therefore EGFR positivity is no reliable surrogate marker for EGFR activity, arguing the need for alternative biomarkers or functional predictive tests.

AB - Overexpression of the epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC) is considered to cause increased EGFR activity, which adds to tumorigenicity and therapy resistance. Since it is still unclear, whether EGFR expression is indeed associated with increased activity in HNSCC, we analyzed the relationship between EGFR expression and auto-phosphorylation as a surrogate marker for activity. We used a tissue micro array, fresh frozen HNSCC tumor and corresponding normal tissue samples and a large panel of HNSCC cell lines. While we observed substantial overexpression only in approximately 20% of HNSCC, we also observed strong discrepancies between EGFR protein expression and auto-phosphorylation in HNSCC cell lines as well as in tumor specimens using Western blot and SH2-profiling; for the majority of HNSCC EGFR expression therefore seems not to be correlated with EGFR auto-phosphorylation. Blocking of EGFR activity by cetuximab and erlotinib points to increased EGFR activity in samples with increased basal auto-phosphorylation. However, we could also identify cells with low basal phosphorylation but relevant EGFR activity. In summary, our data demonstrate that EGFR expression and activity are not well correlated. Therefore EGFR positivity is no reliable surrogate marker for EGFR activity, arguing the need for alternative biomarkers or functional predictive tests.

U2 - 10.1038/s41598-019-49885-5

DO - 10.1038/s41598-019-49885-5

M3 - SCORING: Journal article

C2 - 31537844

VL - 9

SP - 13564

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -