QUANTIFICATION OF INTRATUMORAL VASCULARIZATION PREDICTS METASTASIS IN HUMAN INVASIVE SOLID TUMORS (REVIEW)

There is experimental evidence that tumour invasiveness, progression and metastasis of most solid tumours are angiogenesis-dependent. The onset of the angiogenic tumour cell phenotype behaves as an independent event during malignancy, and the switch from a prevascular to a vascular phase may be achieved by several mechanisms. From experimental data it is reasonable to think that determination of angiogenic activity is a marker of tumour aggressiveness and metastasis in human solid tumours. In particular, determination of tumour angiogenesis seems to be a potential new marker for prognosis, to recognize low versus high risk patients. On the above basis, recently, several clinical studies have been done to correlate the degree of intratumoral vascularisation, detected by immunocytochemical methods, with metastasis and/or prognosis. Overall, the majority of these studies found a significant correlation between microvessel density of the primary tumour and presence of metastasis in the human rumours tested (breast, non-small cell lung, prostatic and head and neck cancers and skin melanoma). Much experience has been obtained for early-stage breast carcinoma. In this tumour, vascular index is emerging as a novel important prognostic tool, particularly useful in identifying high risk node-negative patients eligible for systemic adjuvant therapy. Because angiogenesis-inhibitor drugs are beginning to be used in clinical trials, the knowledge of the individual angiogenic activity of the tumours may be used in the future also as a marker to predict response to such a novel therapeutic approach. The methods to assess tumour vascularisation, clinical results, open questions and future perspectives are presented and discussed.