Assessment of proliferative activity in breast cancer: MIB-1 immunohistochemistry versus mitotic figure count

The proliferative activity is one of the most important single prognostic p arameters in breast cancer diagnosis and the time-honored measure of prolif erative activity, the mitotic figure count, is an integral component of mos t combined prognostic scores. The detection of the cell cycle-specific anti gens Ki-67, and the develop ment of anti-Ki-67 antibodies, including the pa raffin-reactive antibody MIB-1, have established immunohistochemical detect ion of cell cycle-specific antigens as a measure of proliferative activity in breast cancer diagnosis. The current study was performed to correlate mi totic figure counts with. the proliferative activity as assessed by MIB-1 i mmunohistochemistry, taking into consideration the interobserver reliabilit y of 5 pathologists in estimating mitotic figure counts. In 32 consecutive invasive ductal breast carcinomas, mitotic figure counts were performed ind ependently by 5 pathologists. Mitotic activity was expressed as number of m itotic figures per 10 high-power fields and in a 3-tier score according to the Scarff Bloom Richardson system. Immunohistochemistry was performed usin g MIB-1 antibody, heat-induced epitope retrieval, and the standard avidin-b iotin-immunoperoxidase method. MIB-1 immunohistochemistry was assessed in 3 representative 20X fields by semiquantitative estimation (% of tumor cells positive) and by image analysis (number of MIB-1-positive cells/mm(2)). We found a high degree of interobserver correlation among 4 experienced patho logists, in both mitotic figures per 10 high-power fields and the 3-tier sc oring system. We observed significant, albeit weak, correlations between se miquantitative and quantitative MIB-1 immunohistochemistry and the number o f mitotic figures per 10 high-power fields (r between .36 and .53), but thi s significance was lost in 3 of the 5 observers when mitotic activity was e xpressed in the 3-tier scoring system. This study confirms mitotic figure c ounting in the hands of experienced pathologists as a valid, reproducible m eans of assessing proliferative activity in routine breast cancer diagnosis . The statistically significant, albeit only weak, correlation with MIB-1 i mmunohistochemistry is in agreement with results obtained by others and sug gests that MIB-1 immunohistochemistry cannot be translated by a simple conv ersion factor into combined prognostic scores to replace the time-honored m itotic figure counts. Copyright (C) 1999 by W.B. Saunders Company.