Neoangiogenesis and Relationship to Nuclear p53 Accumulation and Vascular Endothelial Growth Factor Expression in Advanced Gastric Carcinoma

Recent studies have shown that tumor suppressor genes, particularly p53, may play a crucial regulatory role in the control of angiogenesis. Accordingly, we analyzed the correlation between p53 accumulation and the expression of vascular endothelial growth factor (VEGF) and microvessel counts in a series of human gastric adenocarcinomas by immunohistochemical staining. p53 expression was absent in 35 cases (29.7%), weak in 34 cases (28.8%), moderate in 35 cases (29.7%), and strong in 14 cases (11.8%). The prognosis of patients with both absent and weak expression of p53 was significantly better than that of patients with both moderate and strong expression of p53. VEGF expression was significantly associated with increased p53 expression. Moreover, increasing expression of p53 significantly correlated with an increase in microvessel counts. Nuclear p53 accumulation may correlate with tumor angiogenesis through VEGF upregulation in gastric carcinomas.

[1]  S. Tsujitani,et al.  Relationship between the expression of vascular endothelial growth factor and the density of dendritic cells in gastric adenocarcinoma tissue. , 1998, British Journal of Cancer.

[2]  P. Boracchi,et al.  Prognostic significance of p53, angiogenesis, and other conventional features in operable breast cancer: subanalysis in node-positive and node-negative patients. , 1998, International journal of oncology.

[3]  A. Kaider,et al.  Tumor angiogenesis in stage IB cervical cancer: correlation of microvessel density with survival. , 1998, American journal of obstetrics and gynecology.

[4]  L. Ellis,et al.  Vessel counts and vascular endothelial growth factor expression in pancreatic adenocarcinoma. , 1998, European journal of cancer.

[5]  Athens Greece,et al.  Comparative evaluation of angiogenesis assessment with anti-factor-VIII and anti-CD31 immunostaining in non-small cell lung cancer. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[6]  K. Maeda,et al.  Combined analysis of p53 and vascular endothelial growth factor expression in colorectal carcinoma for determination of tumor vascularity and liver metastasis , 1997, International journal of cancer.

[7]  S. Tsujitani,et al.  Expression of p21 (waf1/cip1/sdi1), but not p53 protein, is a factor in the survival of patients with advanced gastric carcinoma , 1997, Cancer.

[8]  L. Ellis,et al.  Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer. , 1997, Archives of surgery.

[9]  C. Angeletti,et al.  Neoangiogenesis and p53 protein in lung cancer: their prognostic role and their relation with vascular endothelial growth factor (VEGF) expression. , 1997, British Journal of Cancer.

[10]  K. Dameron,et al.  Sequential development of an angiogenic phenotype by human fibroblasts progressing to tumorigenicity , 1997, Oncogene.

[11]  N. Tanigawa,et al.  Correlation between expression of vascular endothelial growth factor and tumor vascularity, and patient outcome in human gastric carcinoma. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  R. Muraoka,et al.  Tumor vascularity correlates with the prognosis of patients with esophageal squamous cell carcinoma , 1997, Cancer.

[13]  W. Hong,et al.  Retrovirus–mediated wild–type P53 gene transfer to tumors of patients with lung cancer. , 1996, Nature Medicine.

[14]  M. Iki,et al.  Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas. , 1996, Cancer research.

[15]  T. Sawada,et al.  Prognostic value of vascular endothelial growth factor expression in gastric carcinoma , 1996, Cancer.

[16]  D. Mukhopadhyay,et al.  Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression. , 1995, Cancer research.

[17]  C. Cordon-Cardo,et al.  p53 nuclear overexpression: an independent predictor of survival in lymph node--positive colorectal cancer patients. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  M. Toi,et al.  Association of Vascular Endothelial Growth Factor Expression with Tumor Angiogenesis and with Early Relapse in Primary Breast Cancer , 1994, Japanese journal of cancer research : Gann.

[19]  K. Dameron,et al.  Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. , 1994, Science.

[20]  S. Steinberg,et al.  Relationship of p53 overexpression and up-regulation of proliferating cell nuclear antigen with the clinical course of non-small cell lung cancer. , 1994, Cancer research.

[21]  A. Cuschieri,et al.  The prognostic significance of the accumulation of p53 tumour-suppressor gene protein in gastric adenocarcinoma. , 1994, British Journal of Cancer.

[22]  R. Hamazoe,et al.  Intraperitoneal thermochemotherapy for prevention of peritoneal recurrence of gastric cancer. Final results of a randomized controlled study , 1994, Cancer.

[23]  A. Harris,et al.  Clinical prognostic significance of tumour angiogenesis. , 1994, Annals of oncology : official journal of the European Society for Medical Oncology.

[24]  W. Kolch,et al.  Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression. , 1994, Oncogene.

[25]  C. Angeletti,et al.  Relation of neovascularisation to metastasis of non-small-cell lung cancer , 1992, The Lancet.

[26]  A. Harris,et al.  Novel growth regulatory factors and tumour angiogenesis. , 1991, European journal of cancer.

[27]  S. Hirohashi,et al.  Detection of frequent p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single-strand conformation polymorphism analysis. , 1991, Cancer research.

[28]  J. Folkman,et al.  Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. , 1991, The New England journal of medicine.

[29]  W. Bodmer,et al.  p53 mutations in colorectal cancer. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. Bartek,et al.  Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines. , 1990, Oncogene.

[31]  B. Zetter,et al.  Tumor interactions with the vasculature: angiogenesis and tumor metastasis. , 1990, Biochimica et biophysica acta.

[32]  A. Harris,et al.  Increased expression of mutant forms of p53 oncogene in primary lung cancer , 1990, The Lancet.

[33]  J. Folkman What is the evidence that tumors are angiogenesis dependent? , 1990, Journal of the National Cancer Institute.

[34]  A. Levine,et al.  The p53 proto-oncogene can act as a suppressor of transformation , 1989, Cell.

[35]  Peter J. Polverini,et al.  Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene , 1989, Cell.

[36]  A. Levine,et al.  Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life , 1988, Molecular and cellular biology.

[37]  J. Folkman,et al.  How is blood vessel growth regulated in normal and neoplastic tissue? G.H.A. Clowes memorial Award lecture. , 1986, Cancer research.

[38]  N. Tanigawa,et al.  Association of tumour vasculature with tumour progression and overall survival of patients with non-early gastric carcinomas. , 1997, British Journal of Cancer.

[39]  胃癌研究会 Japanese classification of gastric carcinoma , 1995 .

[40]  D. Lane,et al.  p53: oncogene or anti-oncogene? , 1990, Genes & development.

[41]  Bodmer,et al.  p 53 mutations in colorectal cancer ( immunohistokogy / polymerase chain reaction / chemical mismatch cleavage / adenocarcinoma ) , 2022 .