Coexpression of vascular endothelial growth factor and p53 protein in squamous cell carcinoma of the esophagus

OBJECTIVE: p53 plays a role in tumor angiogenesis, and vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The aim of th e present study was to clarify how expression of p53 protein participates i n angiogenesis, and whether the coexpression of VEGF and p53 protein has a significance for angiogenesis and the clinicopathological features in esoph ageal squamous cell carcinoma (SCC). METHODS: Tissues samples were taken from 60 patients with esophageal SCC af ter surgery. The expression of VEGF and p53 protein in these SCC was examin ed immunohistochemically. Microvessel density (MVD) was determined by count ing microvessels in tumor sections stained for Factor VIII-related antigen. Ki-67 labeling index (LI) was calculated, based on Ki-67 antigen immunosta ining, as a proliferative marker. Apoptotic index (AI) was calculated, base d on the terminal deoxynucleotidyl transferase-mediated deoxyuridine tripho sphate biotin nick end labeling, to evaluate apoptosis. RESULTS: VEGF expression was observed in 58.3%, and p53 protein expression was observed in 61.7% of the 60 patients. VEGF and p53 protein were signifi cantly coexpressed in 26 (43.4%). Histological venous invasion (p < 0.01) a nd distant metastasis (p < 0.05) were significantly correlated with p53 pro tein expression. The two parameters were more frequently observed in the SC C with VEGF/p53 coexpression than in those without the coexpression. The MV D and Ki-67 LI were significantly higher (p < 0.01 and p < 0.001), and the AI was significantly lower (p < 0.001) in the SCC with p53 protein expressi on than in the SCC without it. The MVD and Ki-67 LI were higher, and the Al was lower in the SCC with VEGF/p53 coexpression than in those without the coexpression. The 5-yr survival rate in patients with the coexpression was poorer than in the other patients. CONCLUSION: These results suggest that mutant p53 expression is associated with angiogenesis and distant metastasis in esophageal SCC, and that the co expression of p53 and VEGF may play an important role in angiogenesis, and have important clinical significance. (C) 2001 by Am. Cell. of Gastroentero logy.