Tissue Microarray Analyses Suggest Axl as a Predictive Biomarker in HPV-Negative Head and Neck Cancer

TY - JOUR

T1 - Tissue Microarray Analyses Suggest Axl as a Predictive Biomarker in HPV-Negative Head and Neck Cancer

AU - Busch, Chia-Jung

AU - Hagel, Christian

AU - Becker, Benjamin

AU - Oetting, Agnes

AU - Möckelmann, Nikolaus

AU - Droste, Conrad

AU - Möller-Koop, Christina

AU - Witt, Melanie

AU - Blaurock, Markus

AU - Loges, Sonja

AU - Rothkamm, Kai

AU - Betz, Christian

AU - Münscher, Adrian

AU - Clauditz, Till S

AU - Rieckmann, Thorsten

PY - 2022/4/5

Y1 - 2022/4/5

N2 - The receptor tyrosine kinase Axl is described to promote migration, metastasis and resistance against molecular targeting, radiotherapy, and chemotherapy in various tumor entities, including head and neck squamous cell carcinoma (HNSCC). Since clinical data on Axl and its ligand Gas6 in HNSCC are sparse, we assessed the association of Axl and Gas6 expression with patient survival in a single center retrospective cohort in a tissue microarray format. Expression was evaluated manually using an established algorithm and correlated with clinicopathological parameters and patient survival. A number of 362 samples yielded interpretable staining, which did not correlate with T- and N-stage. Protein expression levels were not associated with the survival of patients with p16-positive oropharyngeal SCC. In HPV-negative tumors, Axl expression did not impact patients treated with primary or adjuvant radio(chemo)therapy, but was significantly associated with inferior overall and recurrence-free survival in patients treated with surgery alone. Gas6 was a positive predictor of survival in patients whose treatment included radiotherapy. Associations remained significant in multivariable analysis. Our data question a meaningful contribution of the Axl/Gas6 pathway to radio-resistance in HNSCC and instead suggest that strong Axl expression identifies tumors requiring adjuvant radio(chemo)therapy after surgery.

AB - The receptor tyrosine kinase Axl is described to promote migration, metastasis and resistance against molecular targeting, radiotherapy, and chemotherapy in various tumor entities, including head and neck squamous cell carcinoma (HNSCC). Since clinical data on Axl and its ligand Gas6 in HNSCC are sparse, we assessed the association of Axl and Gas6 expression with patient survival in a single center retrospective cohort in a tissue microarray format. Expression was evaluated manually using an established algorithm and correlated with clinicopathological parameters and patient survival. A number of 362 samples yielded interpretable staining, which did not correlate with T- and N-stage. Protein expression levels were not associated with the survival of patients with p16-positive oropharyngeal SCC. In HPV-negative tumors, Axl expression did not impact patients treated with primary or adjuvant radio(chemo)therapy, but was significantly associated with inferior overall and recurrence-free survival in patients treated with surgery alone. Gas6 was a positive predictor of survival in patients whose treatment included radiotherapy. Associations remained significant in multivariable analysis. Our data question a meaningful contribution of the Axl/Gas6 pathway to radio-resistance in HNSCC and instead suggest that strong Axl expression identifies tumors requiring adjuvant radio(chemo)therapy after surgery.

U2 - 10.3390/cancers14071829

DO - 10.3390/cancers14071829

M3 - SCORING: Journal article

C2 - 35406601

VL - 14

JO - CANCERS

JF - CANCERS

SN - 2072-6694

IS - 7

M1 - 1829

ER -