6th ESACP Congress, Heidelberg, April 7-11, 1999

A104
BALANCE OF CELL PROLIFERATION AND APOPTOSIS IN BREAST CARCINOGENESIS
Mommers ECM, Van Diest PJ, Leonhart AM, Meijer CJLM, Baak JPA
,br> Department of Pathology, Free University Hospital, Amsterdam, Netherlands

In general, progression of pre-invasive to invasive lesions goes hand in hand with a net increase in the number of cells, which may be caused by increased proliferation or decreased cell death. In this study, we determined the mitotic and apoptotic index through a spectrum of pre-invasive ductal breast lesions to invasive carcinoma in search of disturbances in the proliferation /cell death balance in breast carcinogenesis. Seventy two pre-invasive ductal breast lesions and 155 invasive breast carcinomas were used. The number of mitotic (MI) and apoptotic (AI) cells were microscopically counted in hematoxylin and eosin stained sections, and the ratio of the values of MI and AI was calculated (M/A index). A distinction was made between well differentiated and poorly differentiated breast lesions, to arrive at two plausible progression models for breast carcinogenesis. For the well differentiated breast lesions, the MI was rather equal for hyperplasias and well differentiated DCIS, but increased 5-fold from DCIS to well differentiated invasive carcinoma. The AI remained in the same range, resulting in a 3.5-fold increase of the M/A index. For the poorly differentiated breast lesions, a significant increase in MI and AI was found from hyperplasia to poorly differentiated DCIS. From DCIS to poorly differentiated invasive carcinoma, the MI increased and the AI decreased, resulting in a 2.5-fold increase of the M/A index. In conclusion, transition from well differentiated pre-invasive to well differentiated invasive carcinoma is accompanied by an increase of cell proliferation rather than decrease in apoptosis. In contrast, in poorly differentiated breast lesions, decreased apoptosis seems to be equally important as increased proliferation in carcinogenesis and progression.