[In situ determination of the Ki-67 growth fraction (Ki-67 GF) in human tumors (studies in breast cancer)]

Abstract

The monoclonal antibody Ki-67 has been described in 1983 by Gerdes. Lymphocytes stimulated with PHA as well as a number of human tissues have been studied using the antibody. The results have shown, that the Ki-67 antigen is expressed by all cells in the active phases of the cell cycle not, however, by resting cells or the starting sequences of the cell cycle. Although the nature of the Ki-67 antigen ist not yet known, several studies have demonstrated that the Ki-67 growth fraction is a valuable parameter for characterization of malignant tumors. So far, the so-called "Ki-67 growth fraction" (Ki-67 GF) has been determined on non-Hodgkin-lymphomas and on malignant tumors of the bone, kidney and lung. The most extensive data are available on breast cancer. In the author's studies the APAAP-method (APAAP = "alkaline phosphatase-anti-alkaline phosphatase") is preferred as an immunohistochemical staining method. The median Ki-67 growth fraction of 261 breast carcinomas was 12.5% (range 1 to 65%), being five times higher than in benign breast tissue (n = 126). The Ki-67 GF of breast cancer was correlated to different parameters known to be related to prognosis. Thus, a correlation was found with the age of patients, tumor stage, histological grading and hormone receptor status. These results are similar to those obtained by autoradiography and flow cytometry. Of 141 patients the clinical outcome of disease is known (median follow-up 22 months): 25 patients have developed local recurrence of the chest wall. This group of patients showed no significant correlation to the Ki-67 growth fractions of the primary tumors. However, the Ki-67 GF was significantly higher in 20 patients with early systemic disease and in 19 patients who died from breast cancer. Based on these results a clinical trial on adjuvant chemotherapy of lymphnode-negative patients should be taken into consideration. Thus, the prognosis for early stage breast cancer might be improved.