The prognostic value of cell proliferation in colorectal adenomas and carcinomas

Introduction: Colorectal tumorigenesis is a multistep process that begins with the abrogation of normal controls of colorectal mucosa. Aim: Examination of the shift through the adenoma-carcinoma progression sequence of human colon and rectum in context with the expression difference of proliferating cell nuclear antigen (PCNA) between adenoma-carcinoma and adjacent mucosa. Materials and Methods: 178 patients with colorectal polyp-adenoma and/or colorectal carcinoma underwent endoscopic polypectomy or surgical resection. The PCNA expression was examined in 28 non-neoplastic epithelial polyps, 82 neoplastic adenomatous polyps showing different degrees of dysplasia, 12 in situ carcinomas, 6 malignant polyps, 66 colorectal adenocarcinomas. The PCNA protein levels were determined by immunoblot analysis quantified by densitometry. Results: Moving further in the adenoma-carcinoma sequence, difference in the PCNA expression between normal and altered tissue was more frequent. This kind of difference was never found hyperplastic and hamartomatous polyps or inflammatory pseudopolyps. Low difference was found in 2% of tubular and in 6% of tubulo-villous adenomas, and further 6% of the latter had high difference. In mild dysplasia the expression difference was found in 3% of the cases, in moderate it was in 21% and in severe dysplasia the difference was found in 55% of the cases. The expression difference has been 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. Conclusion: These results indicate that PCNA expression difference progressively increased along the sequence from normal mucosa via low grade, middle grade, and high grade dysplasia, adenoma to advanced cancer. The PCNA expression difference is one parameter that contributes to the definition of the degenerative risk and allows selection of patients with high expression difference for constant monitoring.