Clinicopathologic significance of HIF-1 alpha, p53, and VEGF expression and preoperative serum VEGF level in gastric cancer

Sung Yong Oh , Hyuk-Chan Kwon , Sung-Hyun Kim , Jin Seok Jang , Min Chan Kim , Kyeong Hee Kim , Jin-Yeong Han , Chung Ock Kim , Su-Jin Kim , Jin-sook Jeong and Hyo-Jin Kim

BMC Cancer 2008, 8:123doi:10.1186/1471-2407-8-123


Published:	1 May 2008

Abstract (provisional)

Background

Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1 alpha (HIF-1 alpha), p53, and vascular endothelial growth factor (VEGF) are all important factors in the mechanisms inherent to tumor progression. In this work, we have investigated the clinicopathologic significance of HIF-1 alpha, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer.

Methods

We immunohistochemically assessed the HIF-1 alpha, p53, and VEGF expression patterns in 114 specimens of gastric cancer. Additionally, we determined the levels of preoperative serum VEGF (sVEGF).

Results

The positive rates of p53 and HIF-1 alpha (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1 alpha were correlated positively with the depth of invasion (P=0.015, P=0.001, respectively). Preoperative sVEGF and p53 levels were correlated significantly with lymph node involvement (P=0.005, P=0.040, respectively). VEGF overexpression was more frequently observed in the old age group (> 60 years old) and the intestinal type (P=0.013, P=0.014, respectively). However, correlations between preoperative sVEGF level and tissue HIF 1 alpha, VEGF, and p53 were not observed. The median follow-up duration after operation was 24.5 months. HIF-1 alpha was observed to be a poor prognostic factor of disease recurrence or progression (P=0.002).

Conclusions

p53, HIF-1 alpha and preoperative sVEGF might be markers of depth of invasion or lymph node involvement. HIF-1 alpha expression was a poor prognostic factor of disease recurrence or progression in patients with gastric cancers.