Critical analysis of the methods commonly employed in the assessment of cell proliferation: advantages of the NOR silver-staining technique in routine cyto-histopathology.

The methods commonly employed for the assessment of cell proliferation have been critically considered. Some 'historical' techniques, such as the mitotic count and the thymidine labeling index, cannot be proposed for routine pathology because of their complexity and difficult quantification. Other techniques, such as in vitro bromodeoxyuridine incorporation or in vivo bromodeoxyuridine infusion coupled with DNA flow cytometry, permit a very sophisticated analysis of the tumour cell kinetics, but can be performed only in highly specialized centers. During the past few years the immunohistochemical detection of antigens related to the cell cycle--particularly Ki67 or proliferating cell nuclear antigen (PCNA)/cyclin--has been rapidly introduced in numerous laboratories, and, at present, certainly represents the most common method for the assessment of cell proliferation in tumour samples. However, a new marker of cell proliferation has been recently described which presents technical features particularly suitable for routine use: the quantitative evaluation of interphase silver-stained nucleolar organizer regions (AgNORs). The NOR silver-staining technique is simple, very rapidly executed, inexpensive, easily quantifiable and, most important, can be performed on routinely processed cytological and histological samples.