PROLIFERATIVE ACTIVITY OF NORMAL AND NEOPLASTIC UROTHELIUM AND ITS RELATION TO EPIDERMAL GROWTH-FACTOR AND TRANSFERRIN RECEPTORS

Aims-To investigate the proliferative activity (given by the Ki67 inde x) of the normal, atypical, and neoplastic urothelium and its relation to the cellular reactivity for the epidermal growth factor (EGFr) and transferrin (Tfr) receptors. Methods-The Ki67 index and the level of EGFr and Tfr reactivity were determined on frozen sections from 82 pat ients with urothelial cancer. Relevant clinical material was reviewed to establish correlations with the degree of atypia and invasion. Resu lts-Morphologically normal urothelium, whether derived from controls o r patients with cancer, exhibited a low Ki67 index (less than 0.1%) an d weak receptor reactivity. In transitional cell carcinomas (TCCs) the Ki67 index was increased: it ranged between 0.7% and 10% in non-invas ive and exceeded 10% in 88% of the invasive TCCs. Strong positive reac tions for EGFr were seen only in invasive TCCs, but in 47% of invasive TCCs the EGFr was not ''overexpressed'' and did not match the Ki67 in dex. A better correlation was found between the Ki67 index and the Tfr which was positive in 26% of the non-invasive and in 71% of the invas ive tumours. All three variables were increased in severe atypia but v aried considerably in lesser degrees of atypia. Conclusions-Despite th e absence of a close correlation, accelerated growth and enhanced rece ptor expression were characteristic of invasive cancers. These results suggest that the growth rate in TCCs is not causally related to overe xpression of growth factor receptors but that the latter is an abnorma lity which may accompany the malignant phenotype.