Significance of Site-specific Prognosis of Cancer Stem Cell Marker CD44 in Head and Neck Squamous-cell Carcinoma

In several recent studies, CD44 expression has been associated with aggressive behavior in cancers of different types. CD44 expression is also linked to cancer stem cells, which have been shown to play a significant role in tumor progression and poor prognosis in head and neck squamous cell carcinoma (HNSCC), as well as in other cancers. Although CD44 is a potential prognostic marker, it has not been adopted to wider clinical use as a part of treatment planning in HNSCC patients. The aim of this research was to study whether CD44 overexpression is associated with 5year overall survival in HNSCC. We also studied site-specific associations between increased CD44 expression and 5year overall survival. Associations between relative tumor CD44 expressions and smoking, heavy alcohol consumption, histological grade of cancer, TNM staging and HNSCC staging were also studied. In total, 135 paraffin-embedded blocks from HNSCC patients were stained immunohistochemically with a CD44 antibody and were classified by the anatomic location of the tumor. CD44 overexpression had statistically significant association with decreased 5year survival rates when all HNSCC samples were studied (p<0.001). Significant association between intense CD44 expression and poor 5year survival rates was found in the patients with SCC of the oro- and hypopharynx (p<0.001) and the larynx (p=0.042). In patients suffering from HNSCC in the oral cavity, CD44 overexpression did not have a significant effect on overall 5year survival rates. Heavy smoking of over 10 pack years had a significant association with tumor CD44 overexpression (p=0.009). Only pharyngeal (p=0.046) and laryngeal (p=0.047) SCC, but not oral-cavity SCC, had statistically significant associations between heavy smoking and CD44 overexpression when HNSCC was studied in regional groups. Alcohol consumption and tumor grade did not have a significant association with the tumor's CD44 expression. Our results suggest that CD44 overexpression could be used as a sign of aggressiveness, in addition to the HNSCC staging, as a prognostic factor in pharyngeal and laryngeal HNSCC and to assist in treatment selection.