Cancer stem cell biomarkers in locally advanced head and neck squamous cell carcinoma

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OBJECTIVES: To analyze the presence of cancer stem cells markers in consecutive patients with locally advanced Head and Neck Squamous Cell Carcinoma (HNSCC) and establish their suitability as a prognostic biomarker in samples from routine practice. METHODS: Retrospective study of 104 consecutive patients with locally advanced HNSCC treated with definitive surgery and adjuvant chemoradiotherapy. Immunohistochemical expression of CD44, HLA-I, pan-cytokeratin, and phosphorylated Epidermal Growth Factor Receptor (p-EGFR) were evaluated in surgical specimens. Overall Survival (OS) and Disease-Free Survival (DFS) rates were calculated based on clinical characteristics and the total positive score (for tumor marker expression). Hazard ratios were calculated by Cox multivariate analysis. RESULTS: After a median follow-up of 50-months, higher OS rates were observed for patients without cervical node pathological involvement (p < 0.001), patients with HLA-I overexpression and a total positive score ≥ 15% (p = 0.017), and patients with low CD44 expression and a total positive score ≤ 60% (p = 0.022). Grouping by p-EGFR (p = 0.648) or pan-cytokeratin (p = 0.477) expression did not show statistical differences in OS. None of the biomarkers were associated with different DFS rates. Cox multivariate analysis revealed that positive cervical nodes (HR = 1.294; 95% CI 1.025-1.634; p = 0.030) and the expressions of HLA (HR = 0.373; 95% CI 0.168‒0.829; p = 0.015) and CD44 (HR = 2.170; 95% CI 1.031-4.569; p = 0.041) were independently associated with OS. CONCLUSION: Nodal involvement, HLA-I overexpression, and decreased CD44 expression are independent prognostic factors of survival in patients with locally advanced HNSCC. LEVEL OF EVIDENCE: III.

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