Expression of p53 and Vascular Endothelial Growth Factor Associated with Tumor Angiogenesis and Prognosis in Gastric Cancer

Maeda, Kiyoshi; Kang, Soon-Myoung; Onoda, Naoyoshi; Ogawa, Masafumi; Sawada, Tetsuji; Nakata, Bunzo; Kato, Yasuyuki; Chung, Yong‐Suk; Sowa, Michio

doi:10.1159/000011918

Cited by 73 publications

(73 citation statements)

References 18 publications

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“…By contrast, other authors have not shown the association of p53 expression with node metastases or serosal invasion Maeda et al, 1998). Our study agrees with these latter results, since p53 expression did not correlate to a more advanced tumour stage.…”

Section: Discussionsupporting

confidence: 89%

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

et al. 2004

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This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n ¼ 53) or surgery plus adjuvant chemotherapy (n ¼ 103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P ¼ 0.005) and VEGF (P ¼ 0.005) expression were observed. Both MVD X100 (P ¼ 0.05) and positive VEGF expression (Po0.02) were associated with shorter disease-free survival, and positive VEGF expression (P ¼ 0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (Po0.0005 and 0.02, respectively) and overall survival (Po0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P ¼ 0.01).This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.

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Section: Discussionsupporting

confidence: 89%

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

et al. 2004

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“…The direct correlation between p53 and VEGF in colon cancer has already been reported by Takahashy, who suggested that the p53 tumor suppressor gene influenced VEGF expression [37]. Some studies have also showed that aberrant p53 expression is associated with VEGF overexpression in human solid cancers, including colon cancer [38,39], gastric cancer [40] and NSCLC [41,42]. Famulski W. et al also demonstrated the positive correlation between serum levels of p53 and VEGF, and it has been suggested that this is a probable sign of a poor prognosis in colorectal cancer [43].…”

Section: Discussionmentioning

confidence: 67%

Interleukin-17 may be a valuable serum tumor marker in patients with colorectal carcinoma

Radosavljević

Ljujić²,

Jovanović³

et al. 2010

neo

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The promotion of tumor growth is due to a combination of several mechanisms, including angiogenesis and the abundance of cell-derived inflammatory cytokines. The aim of this study was to investigate the serum levels of interleukin 17 (IL-17) and the expression of p53 and Vascular Endothelial Growth Factor (VEGF), in order to determine the relationship between these markers and serum IL-17 levels in patients with colorectal carcinoma.Serum levels of the proinflammatory cytokine IL-17 in patients with colorectal carcinoma (CRC) (n=40) and in a healthy group (n=37) were analysed by ELISA. Surgically resected specimens of 59 colorectal carcinomas were studied by immunohistochemical staining for VEGF and p53.Analyses by ELISA showed significantly higher IL-17 serum levels in patients with colorectal carcinoma than in control subjects (IL-17; mean 128.52±47.62 pg/ml vs. mean 101.91±22.46 pg/ml; p=0.022). We also found an inverse correlation between p53 expression and the level of IL-17 in the serum of patients with CRC. In fact, the serum concentration of IL-17 was significantly higher in patients who did not express p53 (p=0.023). There was no significant correlation between the expression of p53 and VEGF. However, concomitant expression of VEGF and p53 showed a significant correlation with the histological and nuclear grade of the carcinoma.The data presented in our study indicate that IL-17 might act as a valuable tumor marker in patients with CRC and that combined analysis of p53 and VEGF expression might provide additional information about tumor features.

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“…It has been shown that patients with VEGF-overexpressing gastric cancer have shorter tumor-free and overall survival [6,7,8, 14, 15,19,20,21,22,23]. In lymph node-positive resected gastric cancers, the presence of VEGF-D/VEGFR-3 has been shown to be associated with poor survival [24,25,26,27,28,29,30,31].…”

Section: Discussionmentioning

confidence: 99%

“…The prognostic significance of MVD in solid tumors including gastric cancer has been investigated in many studies [13]. Higher MVD scores were shown to be associated with poor outcome in gastric cancer [6,14,15,16]. …”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor, Hypoxia-Inducible Factor 1 Alpha and CD34 Expressions in Early-Stage Gastric Tumors: Relationship with Pathological Factors and Prognostic Impact on Survival

Cabuk

Başaran²,

Çelikel³

et al. 2007

Oncology

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Background: Angiogenesis is one of the key steps in solid tumor growth and metastasis. We planned to investigate the prognostic significance of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) and CD34 expressions as markers of angiogenesis in gastric cancer. Patients and Methods: We retrospectively reviewed the medical records of 51 gastric cancer patients who had total or subtotal gastrectomy at Marmara University Hospital from 1990 to 2004 and evaluated the expression of VEGF, HIF-1α and CD34 by immunohistochemistry in their archival tumor tissues. We recorded the clinical and pathological characteristics of these patients and analyzed their survival outcome. Results: Thirty out of 51 patients were males. The median age was 63 years (range 34–81). The median follow-up was 17 months. Thirty-six patients had node-positive disease. The majority of patients (n = 43) had T2 and T3 disease. Vascular and lymphatic invasions were present in 57 and 77% of tumors, respectively. VEGF and HIF-1α were positive in 65 and 71% of tumors. The median CD34 staining score was 19 (3–68). VEGF, HIF-1α and CD34 expressions were more frequent in tumors without serosal invasion (p = 0.01, p = 0.01 and p = 0.003, respectively). CD34 expression was significantly more frequent in tumors with VEGF and HIF-1α expression (p = 0.00, p = 0.00). HIF-1α expression was more frequent in tumors with VEGF expression (p = 0.00). The 5-year overall survival was 45%. VEGF, HIF-1α, CD34 expressions and other pathological characteristics were found to have no impact on survival. Conclusion: VEGF, HIF-1α and CD34 expressions were more common in tumors without serosal invasion. As a future perspective, biological agents targeting VEGF and HIF-1α might be more effective at earlier stages of gastric cancer.

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Expression of p53 and Vascular Endothelial Growth Factor Associated with Tumor Angiogenesis and Prognosis in Gastric Cancer

Cited by 73 publications

References 18 publications

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

Interleukin-17 may be a valuable serum tumor marker in patients with colorectal carcinoma

Vascular Endothelial Growth Factor, Hypoxia-Inducible Factor 1 Alpha and CD34 Expressions in Early-Stage Gastric Tumors: Relationship with Pathological Factors and Prognostic Impact on Survival

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