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British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Jan;79(2):363–369. doi: 10.1038/sj.bjc.6690058

Expression of vascular endothelial growth factor mRNA in non-small-cell lung carcinomas

G Fontanini 1, L Boldrini 1, S Chinè 1, F Pisaturo 1, F Basolo 1, A Calcinai 1, M Lucchi 2, A Mussi 2, C A Angeletti 2, G Bevilacqua 1
PMCID: PMC2362204  PMID: 9888482

Abstract

The vascular endothelial growth factor (VEGF) has been shown to be strictly related to vascular permeability and endothelial cell growth under physiological and pathological conditions. In tumour development and progression, VEGF plays a pivotal role in the development of the tumoral vascular network, and useful information in the progression of human cancer can be obtained by analysing the vascular endothelial growth factor expression of the tumours. In this study, we investigated the vascular endothelial growth factor transcript expression in non-small-cell lung carcinomas to evaluate the significance of this factor in a group of cancers in which the vascular pattern has been shown to significantly affect progression. Surgical samples of 42 patients with NSCLC were studied using reverse transcription polymerase chain reaction (PCR) analysis and in situ hybridization. Thirty-three out of 42 cases (78.6%) showed VEGF transcript expression predominantly as transcripts for the secretory forms of VEGF (isoforms 121 and 165). In situ hybridization, performed on 24 out of 42 samples, showed that the VEGF transcript expression was in several cases present in the cytoplasm both of neoplastic and normal cells, even if the VEGF mRNA was less expressed in the corresponding non-tumoral part. The VEGF 121 expression was associated with hilar and/or mediastinal nodal involvement (P = 0.02), and, taken together, the VEGF isoforms were shown to significantly influence overall (P = 0.02) and disease-free survival (P = 0.03). As a regulator of tumour angiogenesis, VEGF may represent a useful indicator of progression and poor prognosis in non-small-cell lung carcinomas. © 1999 Cancer Research Campaign

Keywords: vascular endothelial growth factor, non-small-cell lung cancer, reverse transcription polymerase chain reaction, prognosis

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Selected References

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  1. Abu-Jawdeh G. M., Faix J. D., Niloff J., Tognazzi K., Manseau E., Dvorak H. F., Brown L. F. Strong expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in ovarian borderline and malignant neoplasms. Lab Invest. 1996 Jun;74(6):1105–1115. [PubMed] [Google Scholar]
  2. Angeletti C. A., Lucchi M., Fontanini G., Mussi A., Chella A., Ribechini A., Vignati S., Bevilacqua G. Prognostic significance of tumoral angiogenesis in completely resected late stage lung carcinoma (stage IIIA-N2). Impact of adjuvant therapies in a subset of patients at high risk of recurrence. Cancer. 1996 Aug 1;78(3):409–415. doi: 10.1002/(SICI)1097-0142(19960801)78:3<409::AID-CNCR5>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  3. Brown L. F., Berse B., Jackman R. W., Tognazzi K., Guidi A. J., Dvorak H. F., Senger D. R., Connolly J. L., Schnitt S. J. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum Pathol. 1995 Jan;26(1):86–91. doi: 10.1016/0046-8177(95)90119-1. [DOI] [PubMed] [Google Scholar]
  4. Brown L. F., Berse B., Jackman R. W., Tognazzi K., Manseau E. J., Dvorak H. F., Senger D. R. Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol. 1993 Nov;143(5):1255–1262. [PMC free article] [PubMed] [Google Scholar]
  5. DMPA, zalcitabine, and the FDA. Lancet. 1992 Jul 4;340(8810):45–45. [PubMed] [Google Scholar]
  6. Ferrara N. The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat. 1995;36(2):127–137. doi: 10.1007/BF00666035. [DOI] [PubMed] [Google Scholar]
  7. Fontanini G., Bigini D., Vignati S., Basolo F., Mussi A., Lucchi M., Chine S., Angeletti C. A., Harris A. L., Bevilacqua G. Microvessel count predicts metastatic disease and survival in non-small cell lung cancer. J Pathol. 1995 Sep;177(1):57–63. doi: 10.1002/path.1711770110. [DOI] [PubMed] [Google Scholar]
  8. Fontanini G., Vignati S., Boldrini L., Chinè S., Silvestri V., Lucchi M., Mussi A., Angeletti C. A., Bevilacqua G. Vascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma. Clin Cancer Res. 1997 Jun;3(6):861–865. [PubMed] [Google Scholar]
  9. Harpole D. H., Jr, Richards W. G., Herndon J. E., 2nd, Sugarbaker D. J. Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer. Ann Thorac Surg. 1996 May;61(5):1470–1476. doi: 10.1016/0003-4975(96)00104-X. [DOI] [PubMed] [Google Scholar]
  10. Houck K. A., Ferrara N., Winer J., Cachianes G., Li B., Leung D. W. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol. 1991 Dec;5(12):1806–1814. doi: 10.1210/mend-5-12-1806. [DOI] [PubMed] [Google Scholar]
  11. Inoue K., Ozeki Y., Suganuma T., Sugiura Y., Tanaka S. Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma. Association with angiogenesis and tumor progression. Cancer. 1997 Jan 15;79(2):206–213. doi: 10.1002/(sici)1097-0142(19970115)79:2<206::aid-cncr2>3.0.co;2-i. [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. Martiny-Baron G., Marmé D. VEGF-mediated tumour angiogenesis: a new target for cancer therapy. Curr Opin Biotechnol. 1995 Dec;6(6):675–680. doi: 10.1016/0958-1669(95)80111-1. [DOI] [PubMed] [Google Scholar]
  14. Mattern J., Koomägi R., Volm M. Association of vascular endothelial growth factor expression with intratumoral microvessel density and tumour cell proliferation in human epidermoid lung carcinoma. Br J Cancer. 1996 Apr;73(7):931–934. doi: 10.1038/bjc.1996.166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ohta Y., Endo Y., Tanaka M., Shimizu J., Oda M., Hayashi Y., Watanabe Y., Sasaki T. Significance of vascular endothelial growth factor messenger RNA expression in primary lung cancer. Clin Cancer Res. 1996 Aug;2(8):1411–1416. [PubMed] [Google Scholar]
  16. Shibuya M. Role of VEGF-flt receptor system in normal and tumor angiogenesis. Adv Cancer Res. 1995;67:281–316. doi: 10.1016/s0065-230x(08)60716-2. [DOI] [PubMed] [Google Scholar]
  17. Suzuki K., Hayashi N., Miyamoto Y., Yamamoto M., Ohkawa K., Ito Y., Sasaki Y., Yamaguchi Y., Nakase H., Noda K. Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma. Cancer Res. 1996 Jul 1;56(13):3004–3009. [PubMed] [Google Scholar]
  18. Takahashi Y., Cleary K. R., Mai M., Kitadai Y., Bucana C. D., Ellis L. M. Significance of vessel count and vascular endothelial growth factor and its receptor (KDR) in intestinal-type gastric cancer. Clin Cancer Res. 1996 Oct;2(10):1679–1684. [PubMed] [Google Scholar]
  19. Takahashi Y., Kitadai Y., Bucana C. D., Cleary K. R., Ellis L. M. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res. 1995 Sep 15;55(18):3964–3968. [PubMed] [Google Scholar]
  20. Tischer E., Mitchell R., Hartman T., Silva M., Gospodarowicz D., Fiddes J. C., Abraham J. A. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991 Jun 25;266(18):11947–11954. [PubMed] [Google Scholar]
  21. Toi M., Kondo S., Suzuki H., Yamamoto Y., Inada K., Imazawa T., Taniguchi T., Tominaga T. Quantitative analysis of vascular endothelial growth factor in primary breast cancer. Cancer. 1996 Mar 15;77(6):1101–1106. doi: 10.1002/(sici)1097-0142(19960315)77:6<1101::aid-cncr15>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  22. Volm M., Koomägi R., Mattern J. Interrelationships between microvessel density, expression of VEGF and resistance to doxorubicin of non-small lung cell carcinoma. Anticancer Res. 1996 Jan-Feb;16(1):213–217. [PubMed] [Google Scholar]
  23. Wizigmann-Voos S., Breier G., Risau W., Plate K. H. Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomas. Cancer Res. 1995 Mar 15;55(6):1358–1364. [PubMed] [Google Scholar]
  24. Yoshiji H., Gomez D. E., Shibuya M., Thorgeirsson U. P. Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Res. 1996 May 1;56(9):2013–2016. [PubMed] [Google Scholar]

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