Cell proliferation in colorectal adenomas containing invasive carcinoma

Immunohistochemical detection of the nuclear antigen recognised by the monoclonal antibody Ki67, DNA polymerase alpha, and the proliferating cell nuclear antigen (PCNA), and histochemical staining for the argyrophilic proteins associated with the nucleolar organizer regions (AgNOR) were carried out on histological sections from 107 colorectal adenomas containing invasive carcinoma (ACIC), including 7 with regional lymph node metastases. Separate evaluations were made for fields corresponding to adenoma with low-grade dysplasia, adenoma with high-grade dysplasia and early cancer. The same techniques were also employed in 20 cases of normal mucosa and 20 advanced carcinomas. The mean percentages of Ki67, DNA polymerase alpha, and PCNA-positive nuclei and the number of AgNOR per nucleus progressively increased along the sequence from normal mucosa via low-grade and high-grade dysplasia adenoma to advanced cancer, whereas the early cancer values were not significantly different from those in the low-grade dysplasia areas. No significant difference in PCNA positivity and number of AgNOR were noted in ACIC with and without lymph node metastases. It is suggested that the decrease in proliferative activity thus revealed in early cancer may be due to changes in the submucosa microenvironment caused by invasion, and that the metastatic potential of an early colorectal cancer cannot be correlated to such activity.