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. 2004 Jan 12;90(1):206-15.
doi: 10.1038/sj.bjc.6601455.

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

C Fondevila  1 , J P Metges, J Fuster, J J Grau, A Palacín, A Castells, A Volant, M Pera
Affiliations

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

C Fondevila et al. Br J Cancer. .

Abstract

This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n=53) or surgery plus adjuvant chemotherapy (n=103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P=0.005) and VEGF (P=0.005) expression were observed. Both MVD >/=100 (P=0.05) and positive VEGF expression (P<0.02) were associated with shorter disease-free survival, and positive VEGF expression (P=0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (P<0.0005 and 0.02, respectively) and overall survival (P<0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P=0.01). This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.

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Figures

Figure 1
Figure 1
Diffuse-type gastric cancer with signet ring nucleus. (A and B) No expression of p53. (C and D) Intense staining in the irregular nucleus of tumour cells.
Figure 2
Figure 2
Two samples of gastric tumours with expression of VEGF: A (+), B (++). The VEGF appears in the cytoplasm of cells. In (B) the intensity is higher than in (A). The evaluation was carried out in the tumour margins far from the tumour centre where the hypoxia can induce VEGF expression.
Figure 3
Figure 3
Evaluation of tumour angiogenesis. Identification of external border of tumour growth at × 40 (A) and × 100 (B) magnification field: I (desmoplastic stroma), II (infiltration zone), and III (tumour). At × 250 magnification field (C and D), it is possible to appreciate the differences in the degree of MVD between tumours.
Figure 4
Figure 4
(A) Overall survival in patients with VEGF-negative and VEGF-positive tumours (P<0.02). (B) Disease-free survival in patients with VEGF-negative and VEGF-positive tumours (P<0.02).
See this image and copyright information in PMC

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