title: Clinicopathological significance of angiopoietin-like protein 4 expression in oesophageal squamous cell carcinoma.
abstract: BACKGROUND
  Angiopoietin-like protein 4 (ANGPTL4) is involved in regulating glucose homeostasis, insulin sensitivity, angiogenesis and lipid metabolism, and also acts as an apoptosis survival factor for vascular endothelial cells. The protein is also known to be induced in hypoxic environments characteristic of cancer tissue. Recently, ANGPTL4 was shown in cancer cells to facilitate the transendothelial passage of the cells, resulting in distant metastasis. Clinically, venous invasion resulting in distant metastasis is crucial for oesophageal cancer progression.
  
  
  OBJECTIVE
  To determine ANGPTL4 expression and its association with clinicopathological factors and prognosis in human oesophageal squamous cell carcinoma (OSCC).
  
  
  METHODS
  104 cases of surgically-resected OSCC specimens were examined by immunohistochemistry. The association of ANGPTL4 expression with clinicopathological characteristics and postoperative survival rate was statistically analysed.
  
  
  RESULTS
  Expression of ANGPTL4 was statistically correlated with the degree of differentiation, lymphatic invasion and venous invasion. Results of multivariate analysis, performed using multiple logistic regression, showed that lymph node metastasis, lymphatic invasion and ANGPTL4 expression were independent factors predicting venous invasion. Survival rates of patients with ANGPTL4-positive tumours tended to be statistically lower than those with ANGPTL4-negative tumours.
  
  
  CONCLUSIONS
  ANGPTL4 may play an important role in metastasis through lymphovascular invasion, and may potentially affect prognosis.
authors.affiliation: Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Shibata
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirakawa
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Hidaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
mesh_terms: D000368:Aged; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001808:Blood Vessels / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy; D004947:Esophagus / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins