We have reviewed the recent literature on immunohistochemical markers of ce
ll proliferation in normal oral epithelia and leukoplakias. Most findings,
including our own, point to an increased proliferation in oral leukoplakias
that correlates with the degree of dysplasia. Although the basal layer of
normal oral epithelia showed a very low proliferative activity, oral leukop
lakias, even those containing low-grade dysplasia, exhibited a very signifi
cant increase in proliferation. High-grade dysplasia could be clearly diffe
rentiated from both low-grade dysplasia and normal oral epithelia by the pr
esence of proliferating cells in the superficial cell strata, i.e. above or
superficial to the parabasal layer. These changes were detected with sever
al markers including PCNA, Ki-67 (Mib-1), cyclin D1 and CENP-F as well as w
ith procedures using pulse labeling with BrDU, IrDU and tritiated thymidine
. Comparison of all methods showed more similarities than discrepancies. Ne
vertheless, because of its relative simplicity of use and universal accepta
nce in many other sites, Ki-67 (Mib-1) seems to be the most reliable immuno
histochemical marker for future use in cancer prevention and therapeutic cl
inical trials. (C) 2000 Elsevier Science Ltd. All rights reserved.