Abstract

Measurements of cell proliferation can be used as biomarkers of preneoplastic change. In this study, two immunocytochemical methods that measure different components of the cell cycle were compared to assess cell proliferation on biopsy samples from human colonic mucosa. These methods are based on a monoclonal antibody against 5-bromo-2-deoxyuridine (BrdU), which is confined to S phase cells, and a more broad assessment of proliferation based on an antibody against proliferating cell nuclear antigen (PCNA, clone 19A2). In the PCNA assay, only strongly immunostained nuclei were included. The proliferation index was assessed in colonic mucosa from patients with no colonic disorders. Correlation between individual total proliferation indices determined by either method was significant with rs = 0.6 (p < 0.05). The mean proliferation index in the study group was 7.79% using BrdU and 7.64% using PCNA immunocytochemistry. Distribution of labelled cells within crypts was similar with respect to the two methods with a peak at the 18th and the 24th percentile in the case of BrdU and at the 23rd percentile for PCNA. Variance component analysis showed that at least two biopsy specimens should be evaluated per subject to allow a precise individual characterisation. It is concluded that PCNA (19A2) immunocytochemistry may be used as an operational marker of cell proliferation in normal colonic mucosa. A significant correlation and an agreement in the mean proliferation index between PCNA (19A2) and BrdU can only be achieved by a strictly standardised enumeration of labelled cells limited to strongly stained nuclei in the PCNA evaluation.