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Journal of Gastrointestinal Surgery

, Volume 12, Issue 6, pp 1005–1014 | Cite as

Positive VEGF Immunostaining Independently Predicts Poor Prognosis in Curatively Resected Gastric Cancer Patients: Results of a Study Assessing a Panel of Angiogenic Markers

  • Óscar Vidal
  • Antonio Soriano-Izquierdo
  • Manuel Pera
  • José I. Elizalde
  • Antonio Palacín
  • Antoni Castells
  • Josep M. Piqué
  • Alain Volant
  • Jean P. Metges
Article

Abstract

Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) contribute to gastric cancer aggressiveness by up-regulating the expression of proteases. We evaluated the expression and the prognostic significance of angiogenic factors and proteases in 148 patients with R0-resected gastric cancer. Expression of VEGF, Ang-2, cyclooxygenase-2 (COX-2), urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1, matrix metalloproteinases (MMP)-1 and -9 were assayed by immunohistochemistry. After a mean of 63 ± 4 months, 81 out of 148 patients had died due to disease. The probability of being free of recurrence was 62, 48, and 42% at 2, 5, and 10 years, respectively. Single bivariate analysis identified VEGF, Ang-2, COX-2, PAI-1, and MMP-9 expression, along with several clinicopathological parameters (grade of curability, lymph node ratio, pTNM, pT, pN), as variables associated with both decreased disease-specific survival and recurrence. On multivariate analysis, after adjusting for significant clinical covariables, positive VEGF immunostaining was the primary prognostic factor, and no other tumor marker variable could add any significant improvement for the prediction, for both disease-specific survival (p = 0.001; HR, 3.27; 95% CI, 1.76 to 6.10) and tumor recurrence (p = 0.002; HR, 2.81; 95% CI, 1.48 to 5.35). Our study suggests that VEGF alone may be clinically useful for establishing therapeutic decisions in gastric cancer patients.

Keywords

Gastric cancer Prognostic factors Angiogenesis VEGF 

Notes

Acknowledgments

We thank Llorenç Badiella from the Department of Statistics, Universitat Autonoma de Barcelona, for expert help in the statistical analysis and Dr. Alan Cameron and Dr. Joaquim Bellmunt for editorial comments.

This work was supported in part by research grants from the Fundació “la Caixa” (LC 02/126-00, from the Instituto de Salud Carlos III (RC03/02 and RC03/10), and from Fundación Científica de la Asociación Española Contra el Cáncer (Junta Provincial de Albacete).

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Copyright information

© The Society for Surgery of the Alimentary Tract 2007

Authors and Affiliations

  • Óscar Vidal
    • 1
  • Antonio Soriano-Izquierdo
    • 2
  • Manuel Pera
    • 1
    • 6
  • José I. Elizalde
    • 2
  • Antonio Palacín
    • 3
  • Antoni Castells
    • 2
  • Josep M. Piqué
    • 2
  • Alain Volant
    • 4
  • Jean P. Metges
    • 5
  1. 1.Department of Surgery, Institut de Malalties Digestives i Metabolisme, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)University of Barcelona Medical SchoolBarcelonaSpain
  2. 2.Department of Gastroenterology, Institut de Malalties Digestives i Metabolisme, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERehdUniversity of Barcelona Medical SchoolBarcelonaSpain
  3. 3.Department of Pathology, Hospital ClínicUniversity of Barcelona Medical SchoolBarcelonaSpain
  4. 4.Department of PathologyCentre Hospitalier Universitaire Cavale Blanche et MorvanBrestFrance
  5. 5.Department of Medical OncologyCentre Hospitalier Universitaire Cavale Blanche et MorvanBrestFrance
  6. 6.Section of Gastrointestinal SurgeryHospital Universitario del MarBarcelonaSpain

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