Angiogenic interactions of vascular endothelial growth factor, of thymidine phosphorylase, and of p53 protein expression in locally advanced gastric cancer

The assessment of the angiogenic profile of tumors may become an important tool as a guide for the inclusion of novel drugs and molecular therapies in to the standard chemoradiotherapy policy. Several studies have shown the pr ognostic importance of microvessel density (MVD) and of angiogenic factor e xpression in operable gastric cancer. In the present study we investigated, with immunohistochemistry the MVD, the expression of vascular endothelial growth factor (VEGF) and of thymidine phosphorylase (TP) expression, as wel l as the nuclear expression of p53 protein, in a series of patients with lo cally advanced inoperable gastric cancer. A strong association of VEGF with TP expression was noted (P = 0.005), and tumors coexpressing these factors had a statistically higher MVD (P = 0.0001). Nuclear p53 accumulation was also related to a high MVD (P = 0.004); and this was independent of VEGF or TP expression. Microvessel density showed a bell-shaped association with p rognosis; cases with an intermediate MVD exhibit a favorable outcome (P < 0 .05). A trend of nuclear TP expression to define a group of patients with p oorer prognosis was noted (P = 0.06), while none of the remaining variables showed any significant association;The immunostaining results allowed the grouping of the ungiogenic profile in four major categories: 1) highly vasc ularized tumors with VEGF and/or TP expression (about 36% of cases); 2) hig hly angiogenic tumors with p53 nuclear accumulation and low VEGF/TP express ion (7% of cases); 3) poorly vascularized tumor with low VEGF/TP and negati ve nuclear p53 staining (32% of cases); 4) poorly vascularized tumors with TP expression (76 of cases). Specific therapies targeting hypoxia, VEGF, or TP expression as well as p53 gene therapy have entered clinical experiment ation or are already available for clinical use. Using the suggested marker s more than 80% of locally advanced gastric carcinomas can be grouped in di fferent categories according to their angiogenic profile. Such a categoriza tion may be useful for phase III trials on novel therapies targeting the ma jor angiogenesis-related features studied here.