Bromodeoxyuridine uptake and proliferating cell nuclear antigen expression throughout the colorectal tumor sequence

In vitro uptake of bromodeoxyuridine and expression of proliferating cell nuclear antigen (PCNA) were evaluated histochemically in rectal mucosa of control subjects and subjects with colorectal neoplasia in large intestine adenomas and adenocarcinomas. Both labeling indices progressively increased along the path of tumor progression, as did the difference between them (PCNA labeling indices were always greater than those of bromodeoxyuridine). The correlation between them was fairly close in the controls and in adenomas with low-grade dysplasia, whereas no significant linear relations were noted in adenomas with high-grade dysplasia or in adenocarcinomas. The progressive increase in PCNA would thus seem to be related to both hyperproliferation and neoplastic deregulation of PCNA synthesis. In the mucosa of subjects with colorectal neoplasia, PCNA labeling revealed hyperproliferation but not the surface-wards shift of the proliferative compartment detected by bromodeoxyuridine. PCNA expression, therefore, is not a sufficiently sensitive marker of the risk of tumor transformation in the intestinal mucosa.