Where to “cut‐off”?

THE human Ki-67 antigen described by Gerdes et al. in 1983 (1) at present is widely accepted as a prognostic and predictive parameter in clinical oncology. The data characterizing its molecular structure and its role in cell cycle progression indicate that Ki-67 is a key factor in nucleolar rRNA synthesis, and there is a definite relationship between the level of expression of Ki-67 vis-a-vis the entrance of cells into—and advancement through—S phase of the cell cycle. (2) The aim of recently published article in Cytometry Part A by Nies et al. (in this issue, p. 1097; DOI: 10.1002/cyto. a.23564), was to determine the reference values for the fraction of Ki-67-positive cells during maturation of the hematopoetic lineages in normal bone marrow (BM) in relation to the indexes found in hemato-oncological malignancies. The authors of this article evaluated proliferative index for distinct maturation phases during erythro-, myelo-, and mono-poiesis establishing immunophenotypic profiles in combination with the software-based maturation tool (Infinicyt). They demonstrated the heterogeneity of proliferative activity in different cell lineages in BM aspirates of healthy individuals. Whereas the mean value of the total positive Ki-67 fraction in BM was 10.7%, its much higher percentage was seen within the erythroid lineage (70.3%). In the CD34-positive (blast) population, the mean percentage of Ki-67-positive fraction was 58.1%. Relatively modest proliferation activity expressed by Ki-67 21.0% was found for the myeloid total cell population, whereas the monocytic and lymphocytic lineages showed the Ki-67-positive fraction of only 9.7%. Of interest, the range of proliferative indexes in different lineages in the BM of healthy subjects participating in the study was extremely high: for example, the population of Ki-67-positive CD10 lymphocyte progenitor cell varied in the examined material from 13.5 to as much as 43.7%. This knowledge about the proliferative activity in different cell lineages during maturation in normal BM may be of importance for further studies of hematological malignancies. The conclusions of Nies et al. (p. 1097), on the basis of advanced multiparameter flow cytometric measurements using 10-color/12 parameter analysis of BM aspirates from femoral heads of healthy subjects, strikingly differ from the data of Van Bockstaele et al. (3), published 27 years ago in Cytometry (1991). Namely, the latter authors who were using two-color (Ki-67/DNA) flow cytometric approach were unable to detect significant Ki-67 positivity on nuclei from normal BM samples, whereas methodologically it was not possible, at that time, to evaluate Ki-67 expression during the process of cell maturation, it is unclear why no significant presence of Ki67 cells was then detected in BM of normal healthy subjects. Ki-67 is being used in routine clinical pathology to measure the fraction of proliferating cells in different types of human tumors. In patients with prostate cancer, it appears to be a promising marker to assist in discriminating indolent from aggressive tumor (4). Likewise, despite different eligibility criteria, the study design methods for measuring the Ki-67 and the cut-off values the results showing a correlation between Ki-67 expression and prognosis are consistent in