Minichromosome maintenance proteins as biological markers of dysplasia andmalignancy

Dysplasia, an intermediate stage in the progression from normal tissue to n eoplasia, is defined morphologically by a loss of normal orientation betwee n epithelial cells, with changes in cellular and nuclear shape and size. Ho wever, little is known about the functional properties of dysplastic cells, including their replicative state, largely due to a lack of available biol ogical markers. We have used novel antibodies against minichromosome mainte nance (MCM) proteins to examine the proliferative status of a range of hist ological lesions and to characterize dysplastic cells in functional terms. Immunoperoxidase staining was used to localize the MCM proteins, components of the prereplicative complex that is essential for initiating eukaryotic DNA replication. These proteins are down-regulated in cells undergoing diff erentiation or quiescence and, thus, serve as specific markers for prolifer ating cells. In normal and some reactive tissues, MCM expression was present only in res tricted proliferative compartments, consistent with our published findings in the uterine cervix. In dysplastic and malignant tissues, in contrast, MC M proteins were expressed in the majority of cells, extending to surface la yers of dysplastic stratified epithelia, In carcinomas, the frequency of ex pression of MCM proteins showed an inverse correlation with the degree of t umor differentiation, Thus, we suggest that dysplastic cells may be charact erized in functional terms as remaining in cell cycle, due to deregulation of normal controls over cell proliferation. Antibodies against MCM proteins have potential clinical applications, for e xample, in the assessment of tumor prognosis in histological sections and t he identification of proliferating cells in clinical samples using biochemi cal or cytological assays.