In oesophageal squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis

Uchida, Satoshi; Shimada, Yutaka; Watanabe, Go; Tanaka, Hisashi; Shibagaki, Ichio; Miyahara, Tadao; Ishigami, S.; Imamura, Masayuki

doi:10.1038/bjc.1998.281

Cited by 102 publications

(102 citation statements)

References 22 publications

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“…A number of studies have shown a relationship between VEGF expression, or angiogenesis and p53 mutation in human tumors. Some studies showed a positive correlative relationship (25,26), but others did not (27,28). However, no study has yet examined the relationship between p53 overexpression and angiopoietin expression in HCC.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of VEGF and Angiopoietin 2: A Key to High Vascularity of Hepatocellular Carcinoma?

et al. 2003

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Hepatocellular carcinoma (HCC) is becoming one of the most common malignant tumors worldwide and is characterized by a high vascularity. Angiogenesis, formation of new microvessels, is critical for the growth and progression of various human solid tumors. Vascular endothelial growth factor (VEGF) and angiopoietins (Ang1 and Ang2) are endothelial cell-specific vasculogenic and angiogenic growth factors, but their expression and roles in HCC have not been extensively explored. The aim of this study was to determine the expression and cellular localization of VEGF, Ang1, and Ang2 in specimens of resected human HCC using in situ hybridization and immunohistochemical staining and to examine their relationship to microvessel density (MVD) and tumor size. We also investigated whether mutation of p53 protein might affect the expression of the above angiogenic growth factors. VEGF and Ang2 were strongly expressed and localized predominantly to cancer cells, whereas Ang1 was detected in supportive cells of large blood vessels, stromal cells, endothelial cells, and tumor cells. Expression of the VEGF protein and the Ang2 (but not Ang1) mRNA were strongly correlated with MVD (P < .05, P ‫؍‬ .001) and tumor size (P < .05). There was also a strong correlation between VEGF protein and Ang2 mRNA expression (P < .001). However, no significant correlation was found between overexpression of p53 and the expression of VEGF, angiopoietins, or MVD. These findings suggest that overproduction of the angiogenic growth factors VEGF and Ang2 by HCC cells may increase vascularity and tumor growth in a paracrine manner. Our findings also suggest that interaction between VEGF and Ang2 may play a critical role in tumor angiogenesis in HCC.

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Section: Discussionmentioning

confidence: 99%

Overexpression of VEGF and Angiopoietin 2: A Key to High Vascularity of Hepatocellular Carcinoma?

et al. 2003

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“…Its relationship to prognosis also remains unclear. Indeed, according to most of the available studies, VEGF expression significantly predicts a poorer survival (Inoue et al, 1997;Uchida et al, 1998;Koide et al, 1999Koide et al, , 2001Kato et al, 2002). On the contrary, some other recent reports (Ahn et al, 2002;Rosa et al, 2003) are consistent with our results, evidencing a lack of relationship between VEGF expression and clinical outcome in SCCO.…”

Section: Vascular Endothelial Growth Factor In Sccomentioning

confidence: 99%

Diffuse EGFR staining is associated with reduced overall survival in locally advanced oesophageal squamous cell cancer

et al. 2005

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Squamous cell carcinoma of the oesophagus (SCCO) is still a pathology of bad prognosis. Specific therapies are now developed against epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, c-kit receptor (CD117), vascular endothelial growth factor (VEGF) and p53 protein. This study was aimed at assessing their expression in a large series of SCCO, as well as their potential therapeutic interest in this pathology. Immunohistochemical expression of these factors was assessed retrospectively in 107 cases of SCCO with primary surgery, as well as their relationships to recurrence, metastasis and overall survival on a long-term follow-up. Human epidermal growth factor receptor 2 and CD117 were expressed in less than 3% of the cases. Epidermal growth factor receptor and p53 were overexpressed in 68.2 and 66.4% of the cases, and VEGF in 38.3%. Epidermal growth factor receptor overexpression was significantly related to vascular invasion (P ¼ 0.023). Its diffuse positivity was significantly related in multivariate analysis to higher local recurrence (P ¼ 0.006) and lower overall survival (P ¼ 0.003), in a subgroup of patients of poor outcome who had received postoperative adjuvant treatment. These results highlight the great potential prognostic and therapeutic interest of evaluating EGFR diffuse positivity in locally advanced SCCO.

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“…Several studies using multivariate analysis indicated that lymph node metastasis is a strong independent prognostic factor (Theunissen et al, 1991;Roder et al, 1994;Tanigawa et al, 1997). We previously reported that the expression of vascular endothelial growth factor (VEGF) is associated with lymph node metastasis and prognosis in oesophageal cancer (Uchida et al, 1998). Other reports showed that the expression of matrix metalloproteinases (MMPs) (Shima et al, 1992), E-cadherin (Kadowaki et al, 1994;Nakanishi et al, 1997) and p53 (Wang et al, 1994) in primary tumours correlated with lymph node metastasis of oesophageal cancer.…”

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confidence: 99%

Expression of vascular endothelial growth factor, matrix metalloproteinase-9 and E-cadherin in the process of lymph node metastasis in oesophageal cancer

et al. 1999

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Lymph node metastasis is a strong independent prognostic factor for oesophageal cancer. The expression of matrix metalloproteinases (MMPs) and reduction of E-cadherin correlate with lymph node metastasis of oesophageal cancer. We previously reported that the expression of vascular endothelial growth factor (VEGF) is associated with lymph node metastasis. This study was designed to determine whether VEGF, MMP-9 and E-cadherin expression is stable or changes in the process of lymph node metastasis of oesophageal cancer. Using immunohistochemistry, we detected VEGF, MMP-9 and E-cadherin expression in paraffin-embedded specimens of oesophageal squamous cell carcinoma. We classified 134 primary tumours and 174 nodal metastases using two different criteria: the absence [Group N(–)] or presence [Group N(+)] of nodal metastasis, and the stage of metastasis – Early Stage (cancer cells < 50% of lymph node) or Late Stage (≥ 50%) – and compared the expression among two groups and among two stages. The expression rates of Group N(–), Group N(+), Early Stage and Late Stage are as follows: VEGF (49%, 74%, 60%, 33%), MMP-9 (76%, 65%, 95%, 69%) and E-cadherin (49%, 24%, 55%, 38%). VEGF expression was down-regulated in Late Stage lymph node metastasis, while MMP-9 expression was elevated in Early Stage metastasis. E-cadherin expression is restored somewhat in Early Stage metastasis, but suppressed again in Late Stage metastasis. These data suggest that the expression of VEGF, MMP-9 and E-cadherin each change in the process of lymph node metastasis in oesophageal cancer, and that the patterns of change are different. © 1999 Cancer Research Campaign

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In oesophageal squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis

Cited by 102 publications

References 22 publications

Overexpression of VEGF and Angiopoietin 2: A Key to High Vascularity of Hepatocellular Carcinoma?

Overexpression of VEGF and Angiopoietin 2: A Key to High Vascularity of Hepatocellular Carcinoma?

Diffuse EGFR staining is associated with reduced overall survival in locally advanced oesophageal squamous cell cancer

Expression of vascular endothelial growth factor, matrix metalloproteinase-9 and E-cadherin in the process of lymph node metastasis in oesophageal cancer

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