Markers of proliferation in normal and leukoplakic oral epithelia

We have reviewed the recent literature on immunohistochemical markers of cell 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 leukoplakias, even those containing low-grade dysplasia, exhibited a very significant increase in proliferation. High-grade dysplasia could be clearly differentiated from both low-grade dysplasia and normal oral epithelia by the presence of proliferating cells in the superficial cell strata, i.e. above or superficial to the parabasal layer. These changes were detected with several markers including PCNA, Ki-67 (Mib-1), cyclin D1 and CENP-F as well as with procedures using pulse labeling with BrDU, IrDU and tritiated thymidine. Comparison of all methods showed more similarities than discrepancies. Nevertheless, because of its relative simplicity of use and universal acceptance in many other sites, Ki-67 (Mib-1) seems to be the most reliable immunohistochemical marker for future use in cancer prevention and therapeutic clinical trials.