ASSESSMENT OF CELL-PROLIFERATION KINETICS IN FAMILIAL ADENOMATOUS POLYPOSIS BY PCNA IMMUNOSTAINING

Cell proliferation was assessed using immunostaining for proliferative cell nuclear antigen in 10 patients with familial adenomatous polypos is (10 normal-appearing mucosa, 19 adenoma and 3 adenocarcinoma specim ens) and 6 control subjects (rectosigmoid mucosal biopsies). The total labeling index (percentage ratio of the number of labeled cells to th e total number of cells in a column) was 31.70+/-9.32% (mean+/-SD) in adenocarcinoma, 27.95+/-4.24% in adenoma (p<0.001 versus normal-appear ing mucosa), 19.54+/-3.46% in normal-appearing mucosa (p<0.01 versus c ontrol mucosa) and 13.73+/-5.19% in control mucosa. Adenomas showed hy perproliferation and upward expansion of the proliferative zone. When adenomas were classified by size, their diameter was related to the pr oliferative activity (r=0.73, p<0.01). The normal-appearing mucosa alr eady showed changes in cell proliferation. In an animal study, a linea r correlation between the labeling index for proliferative nuclear cel l antigen and that for bromodeoxyuridine was demonstrated in rat colon ic mucosa (r=0.96, p<0.001). These results suggest that immunostaining for proliferative cell nuclear antigen can be used as a convenient an d precise method of studying cell proliferation kinetics and that the increase of the proliferative activity of adenomas in proportion to th eir size provides some support for the adenoma-carcinoma sequence.