In order for some patients to benefit from aggressive chemotherapy for invasive breast
carcinoma, many patients are currently being treated without little or no benefit.
Enormous effort is hence being directed towards the identification of those patients who
will need chemotherapy and those who will not. Since chemotherapy targets proliferating
cells pathologists focus on the proliferative activity of tumors, as assessed by mitotic
figure counts or by cell cycle specific immunohistochemical markers, such as Ki-67 and
H3 histone. As far as the tumor grade is concerned, many of these studies have reported
a tendency to up-grade carcinomas in resection specimen when compared to the initial
diagnosis on the biopsy material, and most studies have noted that the upgrade in
resection specimen is due solely or to a large extent to an increase in the mitotic figure
count. In the present study, we propose a different explanation for the divergence in
mitotic figure counts between biopsy and resection material. We assessed the
proliferative activity of 52 invasive ductal carcinomas and confirm that the number of
mitotic figures significantly increased by a factor of more than 3 in resection specimen
over the biopsy material, while at the same time the pan-cell cycle specific marker MIB-1
yieldes comparable results. we propose that the delayed formalin fixation of resection
specimen allows cell cycle activities to continue for a long time, up to many hours, and that this leads to an arrest of mitoses in metaphase where they are readily identified by
the pathologist. We propose that the mitotic figure count in the rapidly fixed biopsy cores
better represent the tumor biology and should be used as a basis for chemotherapy
therapeutic decisions.