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Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1998 Oct;51(10):771–775. doi: 10.1136/jcp.51.10.771

Expression of vascular endothelial growth factor in human oral squamous cell carcinoma: its association with tumour progression and p53 gene status.

T Maeda 1, S Matsumura 1, H Hiranuma 1, A Jikko 1, S Furukawa 1, T Ishida 1, H Fuchihata 1
PMCID: PMC500933  PMID: 10023341

Abstract

AIMS: To correlate vascular endothelial growth factor (VEGF) expression in oral squamous cell carcinoma with the clinicopathological characteristics and prognosis; and to assess whether p53 gene status is associated with VEGF expression in human cancers. METHODS: Tumour specimens from 45 patients with oral squamous cell carcinomas were examined. Expression of VEGF was determined using an immunohistochemical method, and a tumour was considered positive when more than 5% of the neoplastic cells showed VEGF immunoreactivity. The p53 gene status was screened using a polymerase chain reaction--single strand conformation polymorphism analysis. RESULTS: VEGF positive staining was detected in 19 (42.2%) of the 45 cases. VEGF immunoreactivity did not correlate with the histological degree of tumour differentiation, clinical stages, or lymph node metastasis. The patients with VEGF positive tumours had a significantly worse prognosis than those with VEGF negative tumours. The five year overall survival rate of the VEGF negative patients was 76.5%, as compared with 48.8% for the VEGF positive patients. No significant association between VEGF expression and the p53 gene status of the tumours was found. CONCLUSIONS: VEGF is a good prognostic indicator of the survival of patients with oral squamous cell carcinoma. The p53 gene status does not seem to be associated with VEGF expression in these cancers.

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  1. Anan K., Morisaki T., Katano M., Ikubo A., Kitsuki H., Uchiyama A., Kuroki S., Tanaka M., Torisu M. Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer. Surgery. 1996 Mar;119(3):333–339. doi: 10.1016/s0039-6060(96)80120-6. [DOI] [PubMed] [Google Scholar]
  2. Claffey K. P., Brown L. F., del Aguila L. F., Tognazzi K., Yeo K. T., Manseau E. J., Dvorak H. F. Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res. 1996 Jan 1;56(1):172–181. [PubMed] [Google Scholar]
  3. Dvorak H. F., Brown L. F., Detmar M., Dvorak A. M. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995 May;146(5):1029–1039. [PMC free article] [PubMed] [Google Scholar]
  4. Ferrara N., Winer J., Burton T., Rowland A., Siegel M., Phillips H. S., Terrell T., Keller G. A., Levinson A. D. Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells. J Clin Invest. 1993 Jan;91(1):160–170. doi: 10.1172/JCI116166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar]
  6. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  7. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990 Jan 3;82(1):4–6. doi: 10.1093/jnci/82.1.4. [DOI] [PubMed] [Google Scholar]
  8. Goelz S. E., Hamilton S. R., Vogelstein B. Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. Biochem Biophys Res Commun. 1985 Jul 16;130(1):118–126. doi: 10.1016/0006-291x(85)90390-0. [DOI] [PubMed] [Google Scholar]
  9. Kim K. J., Li B., Winer J., Armanini M., Gillett N., Phillips H. S., Ferrara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 1993 Apr 29;362(6423):841–844. doi: 10.1038/362841a0. [DOI] [PubMed] [Google Scholar]
  10. Levine A. J. The tumor suppressor genes. Annu Rev Biochem. 1993;62:623–651. doi: 10.1146/annurev.bi.62.070193.003203. [DOI] [PubMed] [Google Scholar]
  11. Liotta L. A., Steeg P. S., Stetler-Stevenson W. G. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991 Jan 25;64(2):327–336. doi: 10.1016/0092-8674(91)90642-c. [DOI] [PubMed] [Google Scholar]
  12. Maeda K., Chung Y. S., Ogawa Y., Takatsuka S., Kang S. M., Ogawa M., Sawada T., Sowa M. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer. 1996 Mar 1;77(5):858–863. doi: 10.1002/(sici)1097-0142(19960301)77:5<858::aid-cncr8>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  13. Millauer B., Shawver L. K., Plate K. H., Risau W., Ullrich A. Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature. 1994 Feb 10;367(6463):576–579. doi: 10.1038/367576a0. [DOI] [PubMed] [Google Scholar]
  14. Mukhopadhyay D., Tsiokas L., Sukhatme V. P. Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression. Cancer Res. 1995 Dec 15;55(24):6161–6165. [PubMed] [Google Scholar]
  15. Plate K. H., Breier G., Weich H. A., Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature. 1992 Oct 29;359(6398):845–848. doi: 10.1038/359845a0. [DOI] [PubMed] [Google Scholar]
  16. Relf M., LeJeune S., Scott P. A., Fox S., Smith K., Leek R., Moghaddam A., Whitehouse R., Bicknell R., Harris A. L. Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res. 1997 Mar 1;57(5):963–969. [PubMed] [Google Scholar]
  17. Shweiki D., Itin A., Soffer D., Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992 Oct 29;359(6398):843–845. doi: 10.1038/359843a0. [DOI] [PubMed] [Google Scholar]
  18. Sidransky D., Mikkelsen T., Schwechheimer K., Rosenblum M. L., Cavanee W., Vogelstein B. Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature. 1992 Feb 27;355(6363):846–847. doi: 10.1038/355846a0. [DOI] [PubMed] [Google Scholar]
  19. Toi M., Hoshina S., Takayanagi T., Tominaga T. Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer. Jpn J Cancer Res. 1994 Oct;85(10):1045–1049. doi: 10.1111/j.1349-7006.1994.tb02904.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Toi M., Inada K., Suzuki H., Tominaga T. Tumor angiogenesis in breast cancer: its importance as a prognostic indicator and the association with vascular endothelial growth factor expression. Breast Cancer Res Treat. 1995;36(2):193–204. doi: 10.1007/BF00666040. [DOI] [PubMed] [Google Scholar]
  21. Villuendas R., Piris M. A., Algara P., Sánchez-Beato M., Sánchez-Verde L., Martinez J. C., Orradre J. L., García P., Lopez C., Martinez P. The expression of p53 protein in non-Hodgkin's lymphomas is not always dependent on p53 gene mutations. Blood. 1993 Nov 15;82(10):3151–3156. [PubMed] [Google Scholar]
  22. Volm M., Koomägi R., Mattern J. Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in squamous cell lung cancer. Int J Cancer. 1997 Feb 20;74(1):64–68. doi: 10.1002/(sici)1097-0215(19970220)74:1<64::aid-ijc11>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  23. Weidner N., Folkman J., Pozza F., Bevilacqua P., Allred E. N., Moore D. H., Meli S., Gasparini G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992 Dec 16;84(24):1875–1887. doi: 10.1093/jnci/84.24.1875. [DOI] [PubMed] [Google Scholar]
  24. Weidner N. Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol. 1995 Jul;147(1):9–19. [PMC free article] [PubMed] [Google Scholar]

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