Um. Weisgerber et al., PROLIFERATION CELL NUCLEAR ANTIGEN (CLONE 19A2) CORRELATES WITH 5-BROMO-2-DEOXYURIDINE LABELING IN HUMAN COLONIC EPITHELIUM, Gut, 34(11), 1993, pp. 1587-1592
Measurements of cell proliferation can be used as biomarkers of preneo
plastic change. In this study, two immunocytochemical methods that mea
sure different components of the cell cycle were compared to assess ce
ll proliferation on biopsy samples from human colonic mucosa. These me
thods are based on a monoclonal antibody against 5-bromo-2-deoxyuridin
e (BrdU), which is confined to S phase cells, and a more broad assessm
ent of proliferation based on an antibody against proliferating cell n
uclear antigen (PCNA, clone 19A2). In the PCNA assay, only strongly im
munostained nuclei were included. The proliferation index was assessed
in colonic mucosa from patients with no colonic disorders. Correlatio
n between individual total proliferation indices determined by either
method was significant with r(s)=0.6 (p<0.05). The mean proliferation
index in the study group was 7.79% using BrdU and 7.64% using PCNA imm
unocytochemistry. Distribution of labelled cells within crypts was sim
ilar with respect to the two methods with a peak at the 18th and the 2
4th percentile in the case of BrdU and at the 23rd percentile for PCNA
. Variance component analysis showed that at least two biopsy specimen
s should be evaluated per subject to allow a precise individual charac
terisation. It is concluded that PCNA (19A2) immunocytochemistry may b
e used as an operational marker of cell proliferation in normal coloni
c mucosa. A significant correlation and an agreement in the mean proli
feration index between PCNA (19A2) and BrdU can only be achieved by a
strictly standardised enumeration of labelled cells limited to strongl
y stained nuclei in the PCNA evaluation.