Immunohistochemical evaluation of growth fractions in human breast cancers using monoclonal antibody Ki-67

Abstract

We performed immunohistochemical analyses of 568 breast/cancer specimens using Ki-67, a monoclonal antibody specific for a nuclear antigen present in proliferating cells. The specimens were divided into three groups (I–III) according to the proportion of Ki-positive cells detected. These findings were compared with features of tumor extension as well as with certain prognostic variables. There was no detectable correlation between Ki-67 reactivity and either tumor size or node involvement. In contrast, a statistically significant correlation was found between Ki-67 reactivity and tumor grading, in that G-I tumors had small growth fractions, while a high proportion of G-III tumors exhibited strong (group III) Ki-67 positivity. When growth fractions were compared with biochemical receptor status, a significant difference was detected between tumors with negative and positive findings for receptors. The same co-variation was observed with respect to the overexpression ofneu-protein P185, with mostneu-positive carcinomas being strongly positive for Ki-67 (group III). In the relapse cases examined, there was a close correspondence between Ki-67 reactivity and the duration of the disease-free period. Long-term observation of patients with primary breast carcinoma revealed that, with regard to overall survival, the less reactive groups I and II differed significantly from group III. With respect to disease-free survival, no difference was detectable between Ki-groups II and III, but when these two groups together were compared with group I, a significant trend emerged. Similar results for both overall and disease-free survival were obtained for subgroups of pT2 and G-II carcinomas as well as for receptor expression. Node-negative tumors in the highly reactive group III exhibited a strong trend indicating unfavorable overall survival rates, whereas no such difference was demonstrable with respect to disease-free survival. Node-positive tumors could not be differentiated on the basis of overall survival, but the correlation with growth fraction was significant for disease-free survival. In conclusion, Ki-67 offers a simple and effective method for defining the proliferating cell compartment of breast carcinoma, and may facilitate the assessment of individual tumors as well as efforts to predict the course of disease.