Aberrant Expression of Markers of Cancer Stem Cells in Gastric Adenocarcinoma and their Relationship to Vasculogenic Mimicry

Abstract

<b>Background:</b> Gastric cancer is the second leading cause of cancer-related death in Asia, and the majoritytype is gastric adenocarcinoma (GAC). Most GAC patients die of recurrence and metastasis. Cancer stem cells(CSCs) have been thought to be responsible for the initiation, development, metastasis, and ultimately recurrenceof cancer. In this study, we aimed to investigate expression and clinical significance of CSCs markers, CD133 andLgr5, and vasculogenic mimicry (VM) in primary GAC. Materials and <br/><b>Methods</b>: Specimens from 261 Chinesepatients with follow-up were analyzed for CD133, Lgr5 protein expression and VM by immunohistochemicaland histochemical staining. The Pearson Chi’s square test was used to assess the associations among the positivestaining of these markers and clinicopathological characteristics. Postoperative overall survival time was werestudied by univariate and multivariate analyses. <br/><b>Results</b>: In GAC tissues, positive rates of 49.0%, 38.7%, and26.8% were obtained for CD133, Lgr5, and VM, respectively. The mean score of microvessel density (MVD)was 21.7±11.1 in GAC tissues. There was a significantly difference between the positive and negative groups.There was a positive relationship between the VM, the expression of CD133 and Lgr5, and the score of MVDand the grades of tumor, lymph node metastasis, TNM stages (all p<0.05). The overall mean survival time ofthe patients with CD133, Lgr5, VM, and MVD (≥22) positive expression was lower than that of patients withnegative expression. The score of MVD, positive expression of CD133 and VM were independent prognosticfactors of GAC (p<0.05). <br/><b>Conclusions</b>: VM, and expression of CD133, Lgr5, and the score of MVD are relatedto grades of tumor, lymph node metastasis, TNM stages, and overall mean survival time. It is suggested thatCSCs and VM could play an important role in the evolution of GAC.