Determination of Proliferation Index By MIB‐1 Immunostaining in Early Stage Breast Cancer Using Quantitative Image Analysis

Abstract: Several clinicopathologic variables influence prognosis in breast cancer, including stage, histologic grade, nodal status, and tumor size. Multiple studies have shown an independent value of proliferation index as a prognostic variable for the stratification into favorable and unfavorable groups. The monoclonal antibody MIB‐1 reacts with the same antigen site, not epitope, as recognized by the Ki‐67 antibody. Like Ki‐67, MIB‐1 reacts with cells in the late G1, S, M and G2 phases of the cell cycle, but MIB‐1 has the advantage of reacting with formalin‐fixed, paraffin‐embedded material. The authors investigated the feasibility of using image analysis to quantitate the MIB‐1 antibody staining (proliferation index [PI]) and predict survival in a series of 230 patients with stage I and stage II breast cancer. In a univariate Cox regression model, larger values of MIB‐1 were related to shorter survival times (p < 0.001). Exploratory statistical procedures were used to categorize the patients into good, intermediate, and poor survival groups using the following proliferation indices as cut‐points: <5%, 5–11%, and >11 %, respectively. Higher clinical stage was associated with higher MIB‐1 values and shorter survival (p = 0.01, and p = 0.003, respectively). Tumor size (p = 0.02) and nodal status (p = 0.05) were also associated with higher values of MIB‐1. After adjusting for age, clinical stage, nodal status, and tumor size in a multivariate analysis, MIB‐1 retained its prognostic significance (p < 0.0001) when considered as either a continuous or categorical variable. There were no significant associations between MIB‐1 determined proliferation index and age (p = 0.54), histologic grade (p = 0.69), nuclear grade (p = 0.06) or the presence of vascular invasion (p =.66). There is a strong statistical relationship between cell proliferative activity, as determined by MIB‐1 expression, and survival in early stage breast cancer. Copyright © 1995, Wiley Blackwell. All rights reserved

Duke Scholars

Author Jeffrey R. Marks Surgery, Surgical Sciences