title: Assessment of proliferative activity in breast cancer: MIB-1 immunohistochemistry versus mitotic figure count.
abstract: The proliferative activity is one of the most important single prognostic parameters in breast cancer diagnosis and the time-honored measure of proliferative activity, the mitotic figure count, is an integral component of most combined prognostic scores. The detection of the cell cycle-specific antigens Ki-67, and the development of anti-Ki-67 antibodies, including the paraffin-reactive antibody MIB-1, have established immunohistochemical detection of cell cycle-specific antigens as a measure of proliferative activity in breast cancer diagnosis. The current study was performed to correlate mitotic figure counts with the proliferative activity as assessed by MIB-1 immunohistochemistry, taking into consideration the interobserver reliability of 5 pathologists in estimating mitotic figure counts. In 32 consecutive invasive ductal breast carcinomas, mitotic figure counts were performed independently by 5 pathologists. Mitotic activity was expressed as number of mitotic figures per 10 high-power fields and in a 3-tier score according to the Scarff Bloom Richardson system. Immunohistochemistry was performed using MIB-1 antibody, heat-induced epitope retrieval, and the standard avidin-biotin-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/mm2). We found a high degree of interobserver correlation among 4 experienced pathologists, in both mitotic figures per 10 high-power fields and the 3-tier scoring system. We observed significant, albeit weak, correlations between semiquantitative and quantitative MIB-1 immunohistochemistry and the number of mitotic figures per 10 high-power fields (r between .36 and .53), but this significance was lost in 3 of the 5 observers when mitotic activity was expressed in the 3-tier scoring system. This study confirms mitotic figure counting in the hands of experienced pathologists as a valid, reproducible means of assessing proliferative activity in routine breast cancer diagnosis. The statistically significant, albeit only weak, correlation with MIB-1 immunohistochemistry is in agreement with results obtained by others and suggests that MIB-1 immunohistochemistry cannot be translated by a simple conversion factor into combined prognostic scores to replace the time-honored mitotic figure counts.
authors.affiliation: Department of Pathology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: H A
authors.initials: HA
authors.lastname: Lehr
authors.forename: D A
authors.initials: DA
authors.lastname: Hansen
authors.forename: S
authors.initials: S
authors.lastname: Kussick
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Hwang
authors.forename: F
authors.initials: F
authors.lastname: Krummenauer
authors.forename: S
authors.initials: S
authors.lastname: Trouet
authors.forename: A M
authors.initials: AM
authors.lastname: Gown
mesh_terms: D034961:Antigens, Nuclear; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008940:Mitotic Index; D009687:Nuclear Proteins / Q000378:metabolism*; D015588:Observer Variation
chemical_list: D034961:Antigens, Nuclear; D019394:Ki-67 Antigen; D009687:Nuclear Proteins