Mitotic figure counts are significantly overestimated in resection specimens of invasive breast carcinomas

Abstract

Several authors have demonstrated an increased number of mitotic figures in breast cancer resection specimen when compared with biopsy material. This has been ascribed to a sampling artifact where biopsies are (i) either too small to allow formal mitotic figure counting or (ii) not necessarily taken form the proliferating tumor periphery. Herein, we propose a different explanation for this phenomenon. Biopsy and resection material of 52 invasive ductal carcinomas was studied. We counted mitotic figures in 10 representative high power fields and quantified MIB-1 immunohistochemistry by visual estimation, counting and image analysis. We found that mitotic figures were elevated by more than three-fold on average in resection specimen over biopsy material from the same tumors (20 ± 6 vs 6 ± 2 mitoses per 10 high power fields, P ¼ 0.008), and that this resulted in a relative diminution of post-metaphase figures (anaphase/telophase), which made up 7% of all mitotic figures in biopsies but only 3% in resection specimen (Po0.005). At the same time, the percentages of MIB-1 immunostained tumor cells among total tumor cells were comparable in biopsy and resection material, irrespective of the mode of MIB-1 quantification. Finally, we found no association between the size of the biopsy material and the relative increase of mitotic figures in resection specimen. We propose that the increase in mitotic figures in resection specimen and the significant shift towards metaphase figures is not due to a sampling artifact, but reflects ongoing cell cycle activity in the resected tumor tissue due to fixation delay. The dwindling energy supply will eventually arrest tumor cells in metaphase, where they are readily identified by the diagnostic pathologist. Taken together, we suggest that the rapidly fixed biopsy material better represents true tumor biology and should be privileged as predictive marker of putative response to cytotoxic chemotherapy.

Mitotic Count and the Field of View Area

“…Multiple references suggest counting near the periphery of the tumor as this region has better fixation and should be the more proliferative and invasive. 2,3,10 When strict criteria of field area, counting regions, and mitotic figures are used, consistent results for MC can be obtained.…”

“…The area in which mitotic figures are counted is one of the factors that can be standardized. 1,4,7,10 We prefer the term MC for a static descriptor and propose that MC be determined and reported for 2.37 mm 2 . Furthermore, publications in the veterinary literature need to define more precisely the area in which MC was determined using these terms.…”

“…Therefore 10 hpf ¼ 2.37 mm 2 as our proposed area for MC. Table 1 illustrates calculation of the field area of 10 high-power fields using these parameters and provides guidelines to adjust counts made with different oculars to obtain an area of 2.37 mm 2 . An online source for this information is footnoted with the references.…”

Clinical pathological analysis in 104 ductal breast cancer cases

“…Some scholars believe that cell mitoses represent the biological behavior of the tumor and can make greater value and clinical significance [7]. With the application of computer automatic image analysis technology in the detection of prognostic markers in breast cancer [8][9][10][11][12], the counting method of nuclear fission image now becomes more and more accurately.…”

Clinical Pathological Analysis in 104 Ductal Breast Cancer Cases

“…Some scholars believe that cell mitoses represent the biological behavior of the tumor and can make greater value and clinical significance [7]. With the application of computer automatic image analysis technology in the detection of prognostic markers in breast cancer [8] [9] [10] [11] [12], the counting method of nuclear fission image now becomes more and more accurately.…”