Clinicopathologic significance of HIF-1alpha, 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, Hyo-Jin Kim, 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, Hyo-Jin Kim

Abstract

Background: Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1alpha (HIF-1alpha), 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-1alpha, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer.We immunohistochemically assessed the HIF-1alpha, 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-1alpha (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1alpha 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 (> or = 60 years old) and the intestinal type (P = 0.013, P = 0.014, respectively). However, correlations between preoperative sVEGF level and tissue HIF-1alpha, VEGF, and p53 were not observed. The median follow-up duration after operation was 24.5 months. HIF-1alpha was observed to be a poor prognostic factor of disease recurrence or progression (P = 0.002).

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

Figures

Figure 1
Figure 1
Immunohistochemical staining of HIF-1α, p53, and VEGF. Sites of positive expression of HIF-1α; superficial (a), deep-sited (b), diffuse (c), and vascular invasion (d). Cytoplasmic immunostaining of p53 (e). Underexpression (f) and overexpression (g) of VEGF. Original magnifications: ×200.
Figure 2
Figure 2
Time to progression curve according to HIF-1α expression (P = 0.002).

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