Correlation between MIB‐1 and other proliferation markers

Abstract BACKGROUND Cell proliferation is a major determinant of the biologic behavior of breast carcinoma. MIB‐1 monoclonal antibody is a promising tool for determining cell proliferation on routine histologic material. The objectives of this study were to compare MIB‐1 evaluation to other methods of measuring cell proliferation, with a view to refining the cutoff used to classify tumors with low and high proliferation rates in therapeutic trials. METHODS One hundred eighty‐five invasive breast carcinomas were evaluated for cell proliferation by determining monoclonal antibody MIB‐1 staining, histologic parameters (Scarff–Bloom–Richardson grade and mitotic index) on paraffin sections, S‐phase fraction (SPF) by flow cytometry, and thymidine‐kinase (TK) content of frozen samples. RESULTS There was a high correlation ( P = 0.0001) between the percentage of MIB‐1 positive tumor cells and SPF, TK, histologic grade, and the mitotic index. Multivariate analyses including MIB‐1 at 5 different cutoffs (10%, 15%, 17% [median], 20%, 25%) and the other proliferative markers showed that the optimal MIB‐1 cutoff was 25% and that the mitotic index was the proliferative variable that best discriminated between low and high MIB‐1 samples. A MIB‐1 cutoff of 25% adequately identified highly proliferative tumors. Conversely, with a MIB‐1 cutoff of 10%, few tumors with low proliferation were misclassified. CONCLUSIONS The choice of MIB‐1 cutoff depends on the following clinical objective: if MIB‐1 is used to exclude patients with slowly proliferating tumors from chemotherapeutic protocols, a cutoff of 10% will help to avoid overtreatment. In contrast, if MIB‐1 is used to identify patients sensitive to chemotherapy protocols, it is preferable to set the cutoff at 25%. The MIB‐1 index should be combined with some other routinely used proliferative markers, such as the mitotic index. Cancer 2002;94:2151–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10458