Growth kinetics of colorectal adenoma-carcinoma sequence: an immunohistochemical study of proliferating cell nuclear...

Tumorigenesis is a multistep process that begins with the abrogation of normal controls of cell proliferation. The authors examined the in vitro growth kinetics and compartment shift through the adenoma-carcinoma 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 significantly higher PCNA index than adenomas or control specimens (P = .0001). There also was a difference in the PCNA index between the histological subtypes of adenomas (P = .03), whereas no significant difference 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 shift of cell proliferation toward the middle portion of the colonic glands. The PCNA in the villous, moderate or severe dysplastic, larger or distally located adenomas appeared to be diffuse (P = .04, 0.02, 0.07, and 0.06, respectively). In addition, the transitional mucosa neighboring 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 activity with compartment shift of the proliferating zone through the adenoma-carcinoma sequence. The information essentially supports contemporary understanding of the carcinogenic processes in the human colon.