Vasculogenic Mimicry And Cancer Stem-Like Cell Markers Are Associated With Poor Prognosis Of Non-Small Cell Lung Cancer

Vasculogenic mimicry (VM) is a tumor microcirculation pattern, and it is related to cancer stem-like cell (CSC). However, the clinical significance and prognosis of CSC markers, and VM is not still clear in non-small cell lung cancer (NSCLC). In this study, immunohistochemistry and CD31/PAS double staining were performed to investigate the relationship between epithelial cell adhesion molecule [EpCAM], nestin, CD44, CD34, and VM in 205 patients with NSCLC. The positive expressions of VM, EpCAM, nestin, CD44, and CD34 were 13.66%, 36.59%, 18.05%, 57.07% and 2.93%, respectively. VM was more often detected in large cell lung cancer, poor differentiation, advanced stage, or distant metastasis samples. The VM-positive NSCLC specimens also showed increased expression of nestin, CD44, and CD34, as well as higher MVD, compared with the VM-negative samples. CD34-MVD was significantly different among the three subtypes and was related to VM and nestin. EpCAM was significantly down-expressed in squamous cell carcinoma, non-distant metastasis and good-prognosis specimens. The positive expression of CD44 increased in squamous cell carcinoma, advanced stage, central lung, and male samples. Minimal correlation was found among nestin, CD34, and clinicopathological parameters, except prognosis. The positive expression of both CD34 and nestin showed marked increase in patients who had shorter survival periods. In a conclusion, higher VM, CSCs, and MVD were associated with more aggressive NSCLC. VM, MVD, and some CSC markers were independent unfavorable prognostic factors of NSCLC. CSCs possibly participate in neovascularization in NSCLC.