Proliferation Markers in Breast Carcinoma:Mitotic Figure Count, S-Phase Fraction, Proliferating Cell Nuclear Antigen, Ki-67 and MIB-1

Abstract

Proliferative rate is an important prognostic marker in breast carcinoma. However, the best measurement method has not been established. This study evaluated mitotic figure counts (MFC) as mitoses per 10 high power fields (HPF) and per 1,000 cells, S-phase fraction by flow cytometry, and Ki-67, MIB-1, and proliferating cell nuclear antigen (PCNA) positivity by immunohistochemistry in 135 breast carcinomas. There was strong correlation between the two MFC methods and significant correlation between MIB-1 positivity and all proliferation markers except Ki-67. S-phase fraction showed significant correlation with all proliferation markers except PCNA. Ki-67 positivity correlated only with S-phase fraction, and PCNA positivity only with MIB-1 and mitoses per 10 HPF. High MFC was associated with other prognostic factors: high histologic tumor grade, absence of biochemical and immunohistochemical hormone receptors, and DNA aneuploidy, but not lymph node involvement or tumor size. MIB-1 positivity was also associated with these parameters, except lymph node involvement, tumor size, and DNA aneuploidy. Mitotic figure count and MIB-1 positivity were associated strongly with disease-free survival, up to 46 months. The other proliferation markers were associated with fewer prognostic factors and showed weak or absent association with disease-free survival. The best proliferation markers are mitotic figure counting (either method) or MIB-1 positivity.

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

“…59 -62 Our results were at odds with reports in the literature, including 12 of 12 studies that showed positive correlations were between Ki-67 and mitotic activity 45,47,54,[62][63][64][65][66][67][68][69][70] and 8 of 9 studies that showed a correlation between Ki-67 and SPF. 49,53,[65][66][67][71][72][73] The same results that we produced were reported in the literature concerning Scarff-Bloom grade in 23 of 23 reports, 45-51,53-56,58,65,69 -71,73-79 concerning p53 in 12 of 14 reports, 48,54,58,65,72,75,77,80 -84 and concerning hormone receptor status in 19 of 24 reports. 46 -48,52,54,55,58,62,63,69,70,72,73,76,77,83-86 p21 was not correlated with any clinicopathologic factor or biologic marker.…”

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

“…Different antibodies were used through all trials: anti-Ki-67 was used in 24 studies (52.1%), anti-MIB-1 in 24 studies (52.1%), both antibodies were performed in five studies (Keshgegian and Cnaan, 1995;Veronese et al, 1995;Bevilacqua et al, 1996;Querzoli et al, 1996;Billgren et al, 2002), anti-Ki-S5 in two studies (Rudolph et al, 1999a;Esteva et al, 2004) and anti-Ki-S11 in one study (Rudolph et al, 1999b). The different cut-off values used were those of the authors (range: 3.5 -34%).…”

Ki67 Index in Breast Cancer: Correlation with Other Prognostic Markers and Potential in Pakistani Patients

“…The murine monoclonal antibody Ki-67 reacts with a human nuclear antigen that is expressed in G1, S, G2, and mitosis, but not in G0 (Gerdes et al, 1984). In breast cancer, a strong correlation has been found between the percentage of cells positive for Ki-67 and nuclear grade and mitotic rate (Sahin et al, 1991;Keshgegian 1995).…”