Proliferation index in various stages of breast cancer determined by Ki-67 immunostaining.

To investigate factors involved in progression of breast cancer, we estimated the growth fraction of malignant cell populations in various stages of mammary cancer growth. Frozen sections were immunostained with the Ki-67 monoclonal antibody and the proliferation index determined using static image analysis. Pure intraductal carcinoma, intraductal carcinoma coexisting with invasive disease, and metastatic sites coexisting with primary tumors were studied. The proliferation index of pure intraductal carcinomas (mean 4.5%, median 1.8%) was not significantly different from invasive mammary cancers (mean 5.1%, median 2.2%). The proliferation index determined for the in situ component of primary cancers (mean 3.8%, median 1.5%) was not significantly different from values obtained from the invasive component of growth (mean 4.2%, median 2.1%). Variability between in situ and invasive components for individual cases was minimal in tumors whose proliferation index was less than 3.0%; for tumors with higher proliferation indices, the differences were greater. However, there was no trend toward a decrease or increase in growth fraction for the two components of primary tumor growth. The mean proliferative index for primary tumors (mean 4.9%, median 4.0%) was not significantly different from the mean proliferative score from a matched group of metastatic sites in the same patients (mean 5.7%, median 5.5%). Comparison of individual cases uncovered differences in some tumors; again no consistent trends in either direction were noted. An increase (or decrease) in growth activity does not accompany the transition from intraductal (in situ) disease to invasive mammary cancer, nor does a change in growth fraction necessarily accompany progression of mammary cancer from the primary to regional metastatic site.