The prognostic impact of Axl and Gas6 in head and neck cancer

Introduction The receptor tyrosine kinase Axl is described as a driver for migration and metastasis as well as for resistance against molecular targeting agents and radio- and chemotherapy (RCT) in various tumor entities including head and neck squamous cell carcinoma (HNSCC). For the latter, clinical data describing the impact of Axl and its ligand Gas6 on patient outcome are sparse.

Methods A tissue microarray (TMA) of a heterogeneous HNSCC cohort was stained for Axl and Gas6. The protein expression was classified from the immunohistological staining intensity by an established scoring algorithm. Staining was correlated with clinicopathological parameters and associated with patient survival.

Results Overall 362 samples yielded interpretable staining. Protein expression was neither correlated to T- or N-stage or between both proteins. Axl expression levels had no significant impact on survival in patients with p16-pos. oropharyngeal SCC (OPSCC) irrespective of treatment. In a pooled cohort of patients with laryngeal, hypopharyngeal, and oral cavity SCC as well as p16-neg. OPSCC, Axl expression also did not show a significant impact in patients treated with adjuvant or primary R(C)T. In patients treated solely with surgery, however, strong Axl expression was significantly associated with inferior overall and recurrence free survival. In addition, Gas6 was a positive predictor of survival in patients whose treatment included RT in any form. Both proteins remained independent predictors in multivariable analysis.

Conclusions Our data call into question the capacity of the Axl/Gas6 pathway to confer clinically meaningful radioresistance in HNSCC but rather suggest that strong Axl expression identifies tumors that require adjuvant radio(chemo)therapy after surgery.

Publication History

Article published online:
24 May 2022