GROWTH-KINETICS OF COLORECTAL ADENOMA-CARCINOMA SEQUENCE - AN IMMUNOHISTOCHEMICAL STUDY OF PROLIFERATING CELL NUCLEAR ANTIGEN EXPRESSION

Tumorigenesis is a multistep process that begins with the abrogation o f normal controls of cell proliferation. The authors examined the in v itro growth kinetics and compartment shift through the adenoma-carcino ma sequence of the human colon by determining the labelling indexes of proliferating cell nuclear antigen (PCNA) in normal mucosae (n = 10), adenomas (n = 88), and carcinomas (n = 20). Carcinoma cells had a sig nificantly big-her PCNA index than adenomas or control specimens (P = .0001). There also was a difference in the PCNA index between the hist ological subtypes of adenomas (P = .03), whereas no significant differ ence was observed for dysplastic grade, tumor size, or location (P > . 1). Tubular and tubulovillous adenomas, adenomas with mild dysplasia, small (< 10 mm) adenomas, and proximally located adenomas revealed shi ft of cell proliferation toward the middle portion of the colonic glan ds. The PCNA in the villous, moderate or severe dysplastic,larger or d istally located adenomas appeared to be diffuse (P = .04, 0.02, 0.07, and 0.06, respectively). In addition, the transitional mucosa neighbor ing carcinoma showed an elevation of the mean PCNA index together with an upward shift of cell proliferation compared with the controls (P = .03). These results suggest a stepwise increment of proliferating act ivity with compartment shift of the proliferating zone through the ade noma-carcinoma sequence. The information essentially supports contempo rary understanding of the carcinogenic processes in the human colon. C opyright (C) 1996 by W.B. Saunders Company