Prognostic significance of Ki‐67 and topoisomerase IIα expression in infiltrating ductal carcinoma of the breast

To evaluate the prognostic relevance of Ki‐67 and topoisomerase IIα expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki‐S11 (Ki‐67) and Ki‐S4 (topoisomerase IIα). pS2, c‐erbB2, and p53 were additionally considered as prognostic variables. The median follow‐up time was 149 months. Eight‐hundred‐and‐sixty‐three tumors reacted with Ki‐S11 and Ki‐S the labeling indices of the two antigens were closely associated (r=0.93). Both correlated positively with the tumor size, c‐erbB2, and p53 expression, and negatively with patient age, hormone receptor content, and pS2 immunostaining. In the univariate analysis, Ki‐S11 and Ki‐S4 scores, nodal status, tumor size, tumor grade, and progesterone receptor content strongly predicted both overall and metastasis‐free survival (p <0.00001). Estrogen receptor status, p53, and c‐erbB2 were of minor significance. Concerning overall survival, multivariate Cox regression analysis selected a Ki‐S4 score >25% (p < 0.00001) next to the nodal status, and before tumor size, progesterone receptor content, and patient age. Independent predictors of the occurrence of distant metastases were nodal status, Ki‐S4, tumor size, grade 1, and progesterone receptor negativity, in that order. The Ki‐S11 score was of independent prognostic significance only if examined as a continuous variable. We conclude that topoisomerase IIα expression as assessed by monoclonal antibody Ki‐S4 may add valuable information to current prognostic models for breast cancer. Its predictive value appears to be essentially related to the proliferative activity of tumor cells.