Proliferation markers in non-Hodgkin's lymphoma: A comparative study between cytophotometric quantitation of Ki-67 and flow cytometric proliferation index on fine needle aspirates

Proliferation markers appear to predict biologic behavior and responses to therapy in non-Hodgkin's lymphoma (NHL). We examined the value of the antibody against Ki-67, a marker for cycling cells, in 73 fine needle aspirates and compared these results with parameters of ploidy, DNA, RNA and proliferative index (PI) derived from acridine orange flow cytometry. NHLs were classified into three grades according to the Working Formulation. A fourth miscellaneous group, consisting of atypical lymphoid hyperplasia, was also analyzed. Ki-67 expression was quantitated on a single Cytospin sample from each FNA specimen using an image analysis quantitation software program based on measurement of optical density in the labeled structures. An average of 680 cells distributed through 10 random files was digitized per specimen. The mean Ki-67 positivity and PI calculated for each lymphoma grade were significantly different between grades (P < .0001), while the overall correlation between Ki-67 positivity and PI was high (r = .8). There was no correlation between grade and mean optical density of Ki-67, DNA and RNA, but Ki-67 positivity strongly correlated with PI (r = .8). These results are similar to those of previous studies performed on histologic sections of NHL in which the Ki-67-positive labeling index, measured by either visual scoring or image analysis, correlated positively with increasing grade of lymphoma according to both the Kiel classification and the Working Formulation. We conclude that Ki-67 staining of NHL provides information equivalent to that of PI and is useful for small specimens, such as fine needle aspirates.