Angiogenesis, as evaluated by microvessel density in tumours, has been studied extensively in primary tumours. However, it might play a crucial role also in the development of metastases, an issue that has been less commonly investigated. Also, angiogenesis might well be related to the susceptibility of the tumours to different therapeutic regimens and to their capability of relapsing.

To address these issues we have planned to investigate in four common types of cancer (breast, colon, lung and prostate) the following:

1) Angiogenesis in satellite lymph nodes: we will evaluate the vascular density in the primary tumours and in satellite lymph nodes in both node negative and node positive cases. In the latter, both involved and uninvolved lymph nodes will be investigated. Reactive lymph nodes from patients without neoplastic disease will be investigated as control. In order to differentiate vessels from sinuses present in lymph nodes, several antibodies will be tested.

2) Angiogenesis in residual or relapsing disease after radio/chemiotherapy: we will compare vascular density in primary and relapsing tumours after therapy.

The findings will be correlated with an extensive series of biological parameters, including tumour growth fraction, p53 protein accumulation, p53 gene abnormalities, BCL-2 overexpression, p21 (WAF-1, CIP-1) and p27 immunoreactivity. Also, univariate and multivariate analysis of survival will be done, to ascertain if angiogenesis has independent prognostic value in these human tumours.