Determination of Proliferation Index By MIB-1 Immunostaining in Early Stage Breast Cancer Using Quantitative Image Analysis |
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| Authors: | Lester J. Layfield,M.D., Billie-Jo M. Kerns,B.S.,MT, Debbi H. Conlon. A.A.S.,HT, J. Dirk Iglehart,M.D.,&dagger Jeffrey R Marks,PhD,&dagger Richard K. Dodge,M.S.,&Dagger |
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| Affiliation: | Department of Pathology, Duke University Medical Center, Durham, North Carolina;Department of Surgery, Duke University Medical Center, Durham, North Carolina;Comprehensive Cancer Center Biostatistics, Duke University Medical Center, Durham, North Carolina |
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| Abstract: | 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. |
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