Relationships between vascularization and proliferation in invasive breastcancer

Studies on relationships between angiogenesis and tumour cell proliferation have provided conflicting results. This study has therefore investigated t he relationships between the number and location of fully automatically ide ntified CD31-positive microvessels and interactively segmented mitoses and necrotic compartments by image processing. These features were studied in t en invasive breast cancers, in the 'hot spots' and in whole tumour sections . Microvessel and mitosis hot spots were topographically close or overlappi ng and were always located at the periphery of the tumour. The numbers of m itoses and microvessels per mm(2) in the hot spot were strongly correlated with the respective numbers in the whole tumour section, as well as mutuall y. The ratio of mitoses in the hot spot to the whole tumour section was sig nificantly higher than the corresponding microvessel ratio. Mitoses were pr eferentially located at a distance of 50-150 mu m from microvessels. No sig nificant difference was found between the average distance between mitoses and microvessels in the whole tumour sections and in the hot spot (79 vs. 7 2 mu m), although considerable inter-tumour differences were found (hot spo t 43-101 mu m, tumour 47-111 mu m). The presence of necrotic areas correlat ed with the number of mitoses per mm(2) and necrosis was in general observe d at a distance of more than 150 mu m from the microvessels, suggesting tha t necrotic areas have outgrown their vascular system. These results indicat e the usefulness of image processing of whole tumour sections for the ident ification of proliferation and vascularization hot spots, which are strong prognostic factors in breast cancer. The results also support a close relat ionship between tumour necrosis and microvessels. Copyright (C) 1999 John W hey & Sons, Ltd.