Cdc6p and the members of the minichromosome maintenance (MCM) family of proteins, which associate with the origin-recognition complex (ORC) at initiation of DNA replication, are downregulated and, indeed, absent in quiescent cells. Antibodies recognizing these proteins can therefore be used to detect proliferating cells specifically. In an exciting development, recent research has shown that these observations from basic research can be applied directly to cancer screening.In tissues that normally contain quiescent cells, proliferating cells are characteristic of cancerous and precancerous lesions. However, the visual screening methods frequently used to detect such cells are both time-consuming and difficult to perform accurately as they rely heavily on the identification of subtle differences between cells or of a few abnormal cells among a large population.Antibodies against CDC6 or MCM family proteins therefore have potential applications as a supplement to visual screening for proliferating cells in such tissues by performing antibody staining on the tissue samples. This idea was first tested using antibodies against CDC6 and MCM5 for screening cervical smears and proved very effective1xWilliams, G.H. et al. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 14932–14937Crossref | PubMed | Scopus (242)See all References1 (Fig. 1Fig. 1). More recently, this antibody-based approach has been applied to detecting neoplastic cells from other systems – for example, bladder, breast and colon2xSee all References2 (Fig. 2Fig. 2). As well as providing a valuable supplement to the visual screening assay, the ability to combine this method with fluorescence detection opens up the possibility of automated screening and quantitation in the future. Such advances could well lead to significant improvements in both the scale and reliability of early-cancer screening programmes.FIGURE 1In the standard histological stain (a) of a cervical smear, abnormal nuclei can be difficult to distinguish against the background cells, whereas, with the horseradish peroxidase (HRP)–antibody-enhanced stain detecting MCM5 (b), abnormal nuclei (brown) are readily seen. For further information, see Ref. 1xWilliams, G.H. et al. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 14932–14937Crossref | PubMed | Scopus (242)See all ReferencesRef. 1.View Large Image | Download PowerPoint SlideFIGURE 2Frozen sections of normal colon (a) and adenocarcinoma of the colon (b) stained with an antibody against MCM5 followed by fluorescein-conjugated anti-rabbit antibody (green stain), and propidium iodide (red) for all nuclei. For further information, see Ref. 2xSee all ReferencesRef. 2.View Large Image | Download PowerPoint Slide