THE IMMUNOHISTOCHEMICAL MARKER KI-S2 - CELL-CYCLE KINETICS AND TISSUEDISTRIBUTION OF A NOVEL PROLIFERATION-SPECIFIC ANTIGEN

The monoclonal antibody Ki-S2 binds to a recently characterized prolif eration-specific protein, p100. To assess its distribution pattern und er physiologic and pathologic conditions, we performed immunohistochem ical analyses on an exhaustive spectrum of normal tissues, 624 miscell aneous solid cancers, and 95 hematologic malignancies, and compared th e results with Ki-67 immunostaining on consecutive sections. In additi on, W-SB expression was related to the DNA content by dual parameter n ow cytometric analysis in parallel with Ki-67 labeling using a human c ancer cell line. Immunoreactivity was enhanced at the G(1)/S transitio n and persisted through G(2) and M phase. After adequate antigen retri eval, the antibody was found to yield identical results on fresh and f ormalin-fixed, paraffin-embedded material. The antibody specifically l abeled actively proliferating cells, which constitute a subset of the population recognized by Ki-67, In normal human tissues, Ki-S2 immunol abeling hardly ever exceeded 40% of the Ki-67(+) cell fraction. Immuno reactive scores of the two antibodies exhibited a linear correlation, but statistically significant differences in the ratio of Ki-S2-positi ve to Ki-67-positive cells were nevertheless observed between differen t tissue types. Zn contrast, the ratio of Ki-S2 and Ki-67 immunoreacti ve scores varied widely in neoplastic cells and tissues, occasionally attaining a ratio of almost 1:1. This suggests that loss of growth reg ulatory mechanisms in malignant cells might result in an extreme reduc tion of the G(1) phase fraction and thus in a significantly shorter do ubling time. Therefore, antibody Ki-S2 is likely to allow a more preci se evaluation of the cell fraction that will complete a division cycle and a more confident appraisal of the malignancy potential of a neopl astic process.