Proliferative state of the urothelium with benign and atypical changes. Correlation with transferrin and epidermal growth factor receptors and blood group antigens

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Abstract
We attempted to investigate how the proliferative state of the urothelium correlates with the reactivity for transferrin (Tf) and epidermal grown factor (EGF) receptors and the blood group (BG) antigen. We examined morphologically normal urothelium (34 cases), benign inflammatory and reactive conditions (24 cases), and atypical changes (20 cases) without exophytic or invasive neoplasia. The Ki67 nuclear antigen was used as the proliferation index and was complemented with the in vitro BrdU incorporation assay in 32 cases. The immunohistochemical reactions for Tf and EGF receptors and for the appropriate BG antigen were scored semi-quantitatively on frozen sections. We found that normal urothelium has very low Ki67 and BrdU indices as well as low reactivity for the two receptors and is almost invariably positive for the BG antigen. Benign conditions such as inflammation and metaplasia significantly augment the proliferation indices and the Tf receptor with little change in the EGF receptor and no significant effect on the BG antigen. Moderate atypia includes biologically heterogeneous cases which vary widely in proliferation and receptor expression. Severe atypia-carcinoma in situ is consistently associated with markedly elevated proliferation indices, strong Tf receptor reactivity, and depressed BG antigen. The reactivity for EGF receptor is less consistently increased. Cases with a combination of strong EGF receptor reactions and absence of the expected BG antigen have a poor prognosis with progression to invasive cancer.