METHODOLOGICAL ASPECTS OF USING IMMUNOHISTOCHEMICAL CELL-PROLIFERATION BIOMARKERS IN COLORECTAL-CARCINOMA CHEMOPREVENTION

In vitro uptake of bromodeoxyuridine (BrdU), expression of proliferati ng cell nuclear antigen (PCNA), and expression of antigen Ki-67 as rev ealed by the MIB-1 antibody in fixed and embedded tissues have been re garded as markers of cell proliferation in colorectal tumor progressio n. Proliferation distribution abnormalities in high-risk mucosa have b een illustrated in detail by BrdU labeling of cells in S phase, wherea s PCNA and MIB-1 are less informative at this stage of carcinogenesis. The reliability of BrdU labeling is, in any event, dependent on optim ization of its tissue uptake and diffusion. Neoplastic deregulation of the synthesis and expression of PCNA, coupled with striking variation s in nuclear immunostaining intensity, imposes caution on its use as a n intermediate biomarker in intestinal chemoprevention. Validation of MIB-1 must await the standardization of some of the critical procedure s (e.g., treatment with microwaves) of antigen retrieval. (C) 1994 Wil ey-Liss, Inc.