Positive VEGF immunostaining independently predicts poor prognosis in curatively resected gastric cancer patients: results of a study assessing a panel of angiogenic markers.
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.
Vidal
Oscar
O
Department of Surgery, Institut de Malalties Digestives i Metabolisme, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona Medical School, Barcelona, Spain.
Soriano-Izquierdo
Antonio
A
Pera
Manuel
M
Elizalde
José I
JI
Palacín
Antonio
A
Castells
Antoni
A
Piqué
Josep M
JM
Volant
Alain
A
Metges
Jean P
JP
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D000368:Aged; D042702:Angiopoietin-2 / Q000096:biosynthesis / Q000276:immunology; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000276:immunology; D002452:Cell Count; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005743:Gastrectomy / Q000379:methods*; D005753:Gastric Mucosa / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000276:immunology
D042702:Angiopoietin-2; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A