Uncovering the dynamic relationship between Ki-67 and mitotic indices in breast cancer.

1030 Background: The generation of intra-tumor genetic diversity and metastatic clones relies on frequent passage of cancer cells through error-prone mitoses. Thus, we postulate that low-grade tumors undergo rapid mitotic turnover to drive clonal heterogeneity, while high-grade tumors focus more on their “metastasis program". Metastasis, a multistep dissemination process, requires a phenotypic switch from cell proliferation to migration, since these are mutually-exclusive cellular states. Currently in breast cancer diagnostic practice, the percentage of Ki67-positive "proliferating" cells (Ki67 Index, KI) and number of mitoses/10 high power fields (mitotic index, MI) are evaluated independently and their relationship remains elusive. Here we propose a “mitotic frequency” index (MFI) that rationally combines KI and MI, and provides better prediction of metastatic risk. Methods: The relationship between KI and MI was analyzed retrospectively in pathology reports from 2,500 breast carcinoma cases at Northsid...