Comparison of quantitative and semiquantitative methods of assessing MIB-1 with the S-Phase fraction in breast carcinoma

Different methods of assessing cell proliferation in breast cancer are currently being evaluated. Inherent qualities are required for such methods to be used on a routine basis in a pathology laboratory. Such qualities include high sensitivity and specificity in recognizing proliferating cells, simplicity in execution, and reproducibility. The MIB-1 antibody permits the immunohistochemical detection of the Ki67 antigen in fixed and paraffin-embedded tissue sections. The aim of our study was to compare a semiquantitative and quantitative method of assessing MIB-1 immunostaining with the S-phase fraction (SPF) determined by flow cytometry in a series of 112 breast carcinomas. The median semiquantitative MIB-1 score (SQ.MIB-1) in our series was 27.5%. The median quantitative MIB-1 score (B.MIB-1) was 563 positive neoplastic cells per square millimeter of tumor, and, when corrected by the volume percentage nuclei (C.MIB-1), 2844 positive nuclei per square millimeter of total nuclear area. These three indices were strongly correlated to the SPF (r = 0.73, 0.72, 0.72, n = 78), respectively for SQ.MIB-1, B.MIB-1, and C.MIB-1. MIB-1, assessed quantitatively or semiquantitatively, correlated with the Scarff, Bloom, and Richardson grade, including the mitotic index and nuclear grade, as well as with the progesterone receptor status, SQ.MIB-1 determination was easier and faster than B.MIB-1 and C.MIB-1 determination. A high correlation was found for SQ.MIB-1 results between two observers in this series (r = 0.92, n = 112), but the SQ.MLB-1 repeatability coefficient was 17.6%. Semiquantitation of MIB-1 is strongly correlated to the SPF and is an easy and rapid method of assessing cell proliferation. More studies are necessary for additional assessment of its reproducibility and its prognostic value in breast cancer.