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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