Significance of CD44 expression in head and neck cancer: a systemic review and meta-analysis

Background: CD44 has been reported to be involved with tumor growth and metastasis and has also been implicated as a CSC marker in head and neck squamous cell cancer (HNSCC). However, the prognostic value of CD44 still remains controversial; hence, we investigated the correlation between CD44 and the clinicopathological features of HNSCC by meta-analysis. Methods: A comprehensive search was performed using PubMed, ISI web of Science and China National Knowledge Infrastructure (CNKI) up to April 2013. Only studies with immunohistochemical staining of HNSCC were considered. Data on TNM classification, tumor grade, disease free survival and 3- or 5-year overall survival rate were extracted. Results: Thirty studies with 2102 patients met the inclusion criteria for the meta-analysis. Fifteen studies used anti-pan-CD44 antibody, 9 used anti-CD44-v6 antibody, 2 used anti-CD44-v3 and 2 used anti-CD44s antibody, 1 used anti-CD44-v9, and 1 used anti-CD44-v6,-v3 and -v4-5 simultaneously. The total percentage of CD44 expression was 57.8%, with 49.3% in oral cancer patients, 66.4% in pharynx and 54.7% in larynx cancer patients expressing CD44. No significant correlation between clinical features and CD44 expression was revealed for oral cancer patients, but CD44 was shown to be associated with advanced T categories (larynx: RR = 1.33, 95% Cl 1.01-1.76; larynx & pharynx RR = 1.21, 95% Cl 1.08-1.35), worse N categories (larynx: RR = 2.53, 95% Cl 1.99-3.21; larynx & pharynx RR = 1.95, 95% Cl 1.35-2.82), higher tumor grades (larynx & pharynx RR = 1.71, 95% Cl 1.04-2.79) and 5-year OS rates (larynx: RR = 0.62, 95% Cl 0.47 0.83; larynx & pharynx RR = 0.66, 95% Cl 0.47 0.94) in patients with laryngeal and pharyngolaryngeal cancer. In stratified analysis, pan-CD44 and CD44-v6 expression were both correlated with 5-year OS rate of patients with laryngeal (CD44: RR = 0.66, 95% Cl 0.46-0.95; CD44-v6 RR = 0.53, 95% Cl 0.37-0.77) and pharyngolaryngeal cancer (CD44: RR = 0.56, 95% Cl 0.34-0.93; CD44-v6 RR = 0.53, 95% Cl 0.37-0.77). Conclusions: Our analysis suggested that CD44 is related to worse T category, N category, tumor grade and prognosis, in pharyngeal and laryngeal cancer, but no clear association was revealed between CD44 expression and oral cancer.