Clinical significance of putative cancer stem cell marker CD44 in different histological subtypes of lung cancer

BACKGROUND: According to the cancer stem cell theory, tumors originate from a subset of cells known as cancer stem cells (CSCs) that are responsible for tumor initiation, resistance and relapse. CD44 is a cell adhesion molecule that can aid in the identification of CSCs in various malignancies. OBJECTIVE: The purpose of the current study is to evaluate the expression level and clinical significance of CD44 in lung cancer samples. METHODS: One hundred and ninety-five lung tumor samples including 74 (38%) squamous cell carcinomas (SCC), 61 (31%) adenocarcinomas (ADC), 23 (12%) large cell carcinoma (LCC) in non-small cell lung cancer (NSCLC) group and 37 (19%) small cell lung cancer (SCLC) samples were examined for the expression of CD44 using immunohistochemistry method. The correlation of CD44 expression with clinicopathological parameters as well as Ki-67 status was also assessed. RESULTS: Univariate analysis demonstrated that CD44 expression was significantly higher in NSCLC compared to SCLC (P < 0.001). Among NSCLC, higher level of CD44 expression was found in SCC compared to ADC (P < 0.001) and LCC (P = 0.046). Increased expression of CD44 was significantly correlated with higher grade tumors which correspond to poor prognosis in SCC (P = 0.012) and the lower level of CD44 expression was more often found in well differentiated ADC tumors (P = 0.03). In addition, high expression of CD44 was significantly associated with decreased level of proliferative marker Ki-67 (P = 0.04). CONCLUSIONS: CD44 could be a valuable tool for the study of lung CSCs and provide a novel therapeutic target for treatment of the patients with lung cancer in combination with conventional therapy.