Cellular proliferation in tumors: a review of methods, interpretation, and clinical applications

Cellular proliferation with altered control is one of the 1st characteristics of a neoplastic cell population. Although tumor growth reflects both tumor cell replication and cell loss (opposing growth and antigrowth factors), most studies published in veterinary literature used immunohistochemistry (proliferating cell nuclear antigen [PCNA]; Ki-67 [MIB-1]) or staining for argyrophilic nucleolar organizer regions (AgNORs) to measure proliferation. These studies have appeared in the veterinary literature for more than a decade, describing associations between proliferation indices and histologic grade, biological behavior, and clinical outcome for some tumor types but no clinically relevant associations for other tumors. The results of these studies are summarized here. Methods for evaluation of the numerous regulatory proteins that direct the cell throughout its cycle are now available and should allow more precise identification of cellular aberrations in cancer.