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

Sung Yong Oh¹ , Hyuk-Chan Kwon¹ , Sung-Hyun Kim¹ , Jin Seok Jang¹ , Min Chan Kim² , Kyeong Hee Kim³ , Jin-Yeong Han³ , Chung Ock Kim⁴ , Su-Jin Kim⁴ , Jin-sook Jeong⁴ and Hyo-Jin Kim¹

¹Department of Internal Medicine, Dong-A University College of Medicine, Busan, Republic of Korea

²Department of Surgery, Dong-A University College of Medicine, Busan, Republic of Korea

³Department of Laboratory Medicine, Dong-A University College of Medicine, Busan, Republic of Korea

⁴Department of Pathology, Dong-A University College of Medicine, Busan, Republic of Korea

author email corresponding author email

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


Published:	1 May 2008

Abstract

Background

Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1α (HIF-1α), 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-1α, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer.

We immunohistochemically assessed the HIF-1α, 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-1α (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1α 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 = 0.010, 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-1α, VEGF, and p53 were not observed. The median follow-up duration after operation was 24.5 months. HIF-1α was observed to be a poor prognostic factor of disease recurrence or progression (P = 0.002).

Conclusion

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