<6 months 6-12 months 12-24 months >24 months n = 12 n = 27 n = 10 n = 12

Patients with low thrombospondin-1 expression had higher recurrence rates and decreased overall survival compared to those with moderate or high expression. Interestingly, thrombospondin-1 expression remained an independent prognostic factor of tumour recurrence and overall survival in the presence of tumour stage and tumour grade. Thrombospondin-1 expression was significantly associated with microvessel density in this study but also correlated with nuclear p53 accumulation.33 These results suggest that p53 may also affect tumour angiogenesis by regulating thrombospondin-1 expression.

With regard to these observations, molecules involved in tumour angiogenesis may not only be promising predictors of disease outcome, but also serve as interesting targets for gene therapy. As several angiogenesis inhibitors are currently investigated in a variety of solid tumours in phase I/II trials, these concepts approach clinical reality.34

Decreased cell adhesion and motility of the tumour cell are other fundamental requirements for the aquisition of invasive properties. Selectins, integrins and cadherins are those substances responsible for cell/ cell contact and interaction. Thus, a subsequent loss of adhesion molecules will be associated with an increased capability of a given cell to leave the cellular formation and invade the surrounding tissue.

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