title: Aberrant Expression of Markers of Cancer Stem Cells in Gastric Adenocarcinoma and their Relationship to Vasculogenic Mimicry.
abstract: BACKGROUND
  Gastric cancer is the second leading cause of cancer-related death in Asia, and the majority type 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 recurrence of cancer. In this study, we aimed to investigate expression and clinical significance of CSCs markers, CD133 and Lgr5, and vasculogenic mimicry (VM) in primary GAC.
  
  
  METHODS
  Specimens from 261 Chinese patients with follow-up were analyzed for CD133, Lgr5 protein expression and VM by immunohistochemical and histochemical staining. The Pearson Chi's square test was used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time was were studied by univariate and multivariate analyses.
  
  
  RESULTS
  In GAC tissues, positive rates of 49.0%, 38.7%, and 26.8% 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 MVD and the grades of tumor, lymph node metastasis, TNM stages (all p<0.05). The overall mean survival time of the patients with CD133, Lgr5, VM, and MVD (≥22) positive expression was lower than that of patients with negative expression. The score of MVD, positive expression of CD133 and VM were independent prognostic factors of GAC (p<0.05).
  
  
  CONCLUSIONS
  VM, and expression of CD133, Lgr5, and the score of MVD are related to grades of tumor, lymph node metastasis, TNM stages, and overall mean survival time. It is suggested that CSCs and VM could play an important role in the evolution of GAC.
authors.affiliation: Department of Pathology, the First Hospital Affiliated to Bengbu Medical College, Bengbu Medical College, Bengbu, Anhui Province, China E-mail : honghongwuwu@sohu.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.forename: Zhen-Zhong
authors.initials: ZZ
authors.lastname: Feng
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Gong
authors.forename: Ze-Nong
authors.initials: ZN
authors.lastname: Cheng
authors.forename: Nan
authors.initials: N
authors.lastname: Yao
authors.forename: Dan-Na
authors.initials: DN
authors.lastname: Wang
authors.forename: Shi-Wu
authors.initials: SW
authors.lastname: Wu
mesh_terms: D000071916:AC133 Antigen; D000230:Adenocarcinoma / Q000098:blood supply / Q000737:chemistry* / Q000556:secondary*; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010455:Peptides / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000032:analysis; D013270:Stomach / Q000737:chemistry; D013274:Stomach Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology*; D015996:Survival Rate
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015820:Cadherins; D006023:Glycoproteins; C116884:LGR5 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; D043562:Receptors, G-Protein-Coupled