Clinicopathological significance of angiopoietin-like protein 4 expression in oesophageal squamous cell carcinoma

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. AIMS: 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.