Relationship between cell proliferation pattern and the adenoma-carcinoma progression sequence of human colorectum

Introduction: During the colorectal carcinogenesis proliferating cell nuclear antigen (PCNA) plays a key role.

Aim: Relation of PCNA expression difference between adenoma-carcinoma and the adjacent normal mucosa to the shift through the adenoma-carcinoma progression sequence of human colorectum. Materials and methods: PCNA expression was examined by immunoblot and densitometry in 106 polyps, 12 in situ carcinomas, 91 colorectal adenocarcinomas and their adjacent mucosa specimens.

Results: Moving further in the adenoma-carcinoma sequence, difference in the PCNA expression between normal and altered tissue was more frequent. There was no difference found in hyperplastic and hamartomatous polyps or inflammatory pseudopolyps. In 2% of tubular and in 6% of tubulo-villous adenomas low difference was found, and further 6% of the latter had high difference. The degree of dysplasia of villous adenomas correlated with the frequency of difference. In mild dysplasia expression difference was found in 3%, in moderate in 21%, and in severe dysplasia in 55% of the cases. It was found in 57% of in situ carcinomas grown on base of a polyp, and in 69% of the malignant polyps. In adenocarcinomas, the Dukes classification paralleled well with PCNA expression difference between tumor – peritumoral mucosa, in contrast with the only in tumor measured PCNA expression. Conclusion: These results indicate that PCNA expression difference between normal and altered tissue progressively increased along the sequence from normal mucosa via low grade, middle grade, and high grade dysplasia, adenoma to advanced cancer.