title: Deregulation of the cell polarity protein Lethal giant larvae 2 (Lgl2) correlates with gastric cancer progression.
abstract: BACKGROUND
  We investigated the roles of Lethal giant larvae 2 (Lgl2), an epithelial cell polarity protein, during gastric carcinogenesis and gastric cancer (GC) progression and evaluated the correlation of Lgl2 with epithelial-mesenchymal transition (EMT) markers.
  
  
  METHODS
  Lgl2 protein and mRNA expression were determined by immunohistochemistry and mRNA in situ hybridization in a large series of GC and preneoplastic lesions. Additionally, expression of 7 EMT markers was examined by immunohistochemistry.
  
  
  RESULTS
  Loss of membrane Lgl2 staining in GC was observed in 347 of 409 GCs. Lgl2 loss was associated with diffuse histological type (P < 0.001), advanced stage (P = 0.021), and worse prognosis (P = 0.047). Furthermore, Lgl2 loss correlated with reduced E-cadherin expression (P < 0.01) and increased expression of vimentin (P < 0.01). Combined analysis of Lgl2 and the EMT markers, S100A4 and MMP2, improved predictions of patient outcomes. During gastric carcinogenesis, membrane expression of Lgl2 was progressively lost in 4 % of normal mucosa, 75 % of intestinal metaplasia, 58 % of gastric dysplasia, 69 % of intestinal type GC, and 96 % of diffuse type GC.
  
  
  CONCLUSIONS
  Our results suggest that Lgl2 loss occurs at an early stage of gastric carcinogenesis and contributes to GC progression.
authors: Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea.
authors: Kyung Han
authors: KH
authors: Nam
authors: Min A
authors: MA
authors: Kim
authors: Gheeyoung
authors: G
authors: Choe
authors: Woo Ho
authors: WH
authors: Kim
authors: Hye Seung
authors: HS
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C526122:llgl2 protein, human; C077591:S100A4 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2