The predictive role of Axl and Gas6 in patients with squamous cell carcinoma of the head and neck

Introduction Head and neck squamous cell carcinoma (HNSCC) represent a heterogeneous entity with regard to localisation, outcome and biology. Especially for locally advanced HPV-negative tumors there is still a poor prognosis despite all therapeutic advances. Currently the HPV/p16-status in oropharyngeal tumors is the only established prognostic marker. Predictive markers that would provide guidance for therapeutic decision making are completely missing. Potential candidates for such markers are the receptor tyrosine kinase Axl and its ligand Gas6.

Methods A tissue micro array (TMA), containing more than 500 HNSCC samples, was stained for Axl and Gas6. The immunohistological staining of the tissue samples was scored by intensity (0 (negative), 1 (weak), 2(moderate), 3(strong)) and the percentage of tumor cells stained by an established algorithm. Staining was associated with patient survival.

Results For Axl we observed a heterogeneous outcome depending on the localisation. While a low staining intensity (0&1) was associated with poor survival in patients with hypopharyngeal/laryngeal tumors (OS: p = 0.047), we observed poor survival at maximum staining intensity (3) in p16-neg. oropharyngeal tumors (OS: p = 0.0033). The Gas6 staining intensity was mostly negative or weak. The maximum staining intensity was 2 (moderate). This subgroup showed a favorable survival (OS: p = 0.029) and was based on patients with R(C)T-treatment (primary or adjuvant, OS: p = 0.028).

Conclusions Increased Axl expression represents a potential negative predictive marker in patients with p-16 neg. oropharyngeal tumors and increased expression of Gas6 a potential positive predictive marker of survival.

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Publication History

Article published online:
10 June 2020