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

Abstract

BackgroundHypoxia 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).ResultsThe 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).Conclusionp53, 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.

Measurement of circulating levels of VEGF-A, -C, and -D and their receptors, VEGFR-1 and -2 in gastric adenocarcinoma

“…The correlation of markers of angiogenesis and clinico-pathological features further highlights the complex interaction between various factors and their respective receptors [16,23] . Whereas VEGF-A and -D did not correlate with any of the clinico-pathological features studied, it is interesting to note the strong association between VEGFR-1 and advanced stage cancer, the presence of metastasis, and poor tumor differentiation.…”

“…Among angiogenic stimulators, VEGF-A plays an essential role in both vasculogenesis and angiogenesis [14] . Serum concentrations of VEGF-A have been examined in patients with gastric cancer and a relationship between the serum concentration of VEGF and metastasis and/or poor outcome has been demonstrated [15,16] . However, the significance of other VEGF family members (VEGF-B, -C, and -D) in tumor angiogenesis and metastasis are not fully demonstrated [17] .…”

Gene Expression Profiling of Fixed Tissues Identified Hypoxia-Inducible Factor-1α, VEGF, and Matrix Metalloproteinase-2 as Biomarkers of Lymph Node Metastasis in Hepatocellular Carcinoma

“…Heatmaps are shown in Figure 1. On the basis of previous reports (17,(20)(21)(22)(23), we chose HIF-1a, VEGF, and MMP-2 for further analysis. Immunohistochemistry and TMA analyses of these proteins were conducted with an independent cohort of 309 HCC patients to evaluate the ability of these potential biomarkers to predict LNM.…”

Dietary glycemic load and gastric cancer risk in Italy

“…Insulin increases the activity of IGFs, such as IGF-1 (Gnagnarella et al, 2008), and suppresses hepatic secretion of IGF-binding protein-1. IGF-1 stimulates cell proliferation and differentiation, inhibits apoptosis (Kaaks and Lukanova, 2001;Gnagnarella et al, 2008) and increases production of vascular endothelial growth factors, important in tumour angiogenesis, and the expression of glucose transporters, glycolytic enzymes, and growth factors, which may promote tumor cell survival under hypoxic conditions (Akakura et al, 2001;Oh et al, 2008). Higher IGF-1 concentrations have been observed in patients with gastric cancer than in healthy controls (Franciosi et al, 2003).…”