Membrane changes during urothelial hyperplasia and neoplasia

Normal mammalian urothelium has a complex pattern of morphogenesis and cell differentiation. The luminal face of the polyploid, superficial cells is limited by a morphologically unique plasma membrane with a highly ordered substructure. This membrane is a convenient marker for normal differentiation in the urothelium. In reversible, benign hyperplasia, following cytotoxic damage, the luminal face of the most superficial layer of cells is limited by an undifferentiated membrane which is comparable to the plasma membrane of normal basal cells. When the hyperplasia regresses, normal differentiation of the urothelium is reestablished, and the normal, specialized surface membrane is again produced. In both preneoplastic hyperplasia and early neoplasia induced by various carcinogenic regimens, a novel form of differentiation affecting the surface membrane is seen in some superficial cells. Microvilli form on their free luminal face and are limited by a membrane with an unusual, structured glycocalyx, which is not found in normal urothelium or benign hyperplasia. This glycocalyx also develops on some cells in transitional cell carcinoma of the bladder in man. This novel glycocalyx may be a morphological marker for neoplastic transformation in the urothelium.