SCANNING IMMUNOELECTRON MICROSCOPY OF NORMAL AND NEOPLASTIC HUMAN URINARY BLADDER

Abstract

The surface morphology of normal and neoplastic human bladder epithelium has been examined by scanning electron microscopy (SEM) and the blood group ABH isoantigens (IA) have been studied by scanning immunoelectron microscopy using bacteriophage T₄ (T₄) as a marker.
Microridges, short microvilli and microplicae were present on the surface of normal epithelium. The trigone epithelial cells were dominated by microplicae and distinguished from the cells of other anatomical regions. IA were distributed uniformly on the luminal surface of the normal bladder epithelium, showing some differences of labeling intensity in different anatomical regions.
Inflammatory condition did not induce essential changes in the distribution of IA, although considerable changes in the surface morphology occurred.
Neoplastic transformation induced drastic alterations both in the surface morphology and in the distribution of IA. The existence of pleomorphic microvilli, as observed in most of neoplastic bladder epithelium, was a most distinctive feature of malignant tumors and provided a surface marker of irreversible neoplastic transformation. Based on the altered surface appearence, pleomorphism of microvilli and the degree of attachment to the surrounding cells, tumor cells were classified into 5 main SEM cell types; Type 1: Cells with short microvilli and microridges. Type 2: Cells with uniformly distributed least pleomorphic microvilli. Type 3: Cells covered evenly with moderately pleomorphic microvilli and smooth surface cells. Type 4: Cells with highly pleomorphic microvilli gathering or fusing each other. Some of these cells had blebs and membrane ruffles. Type 5: Round small cells with poor cell-to-cell contact. Most of these cells had highly pleomorphic microvilli and blebs and some of them had smooth surface.
There was a high degree correlation between these cell types and histological grade; grade I consisted of types 1, 2, and 3, grade II of types 2, 3, and 4 and grade III of types 3, 4, and 5. The degree of the deletion of IA expression was correlated with histological grade. In the grade I lesions 23% were negative for IA, in the grade II 71% were negative, and in the grade III IA could not be detected. With regard to the relation between SEM cell type and IA expression, IA were preserved in all cases of type 1, while IA were deleted in all cases of type 2 and type 5. In types 3 and 4, the rate of deletion of IA was 50% and 73%, respectively.
The deletion of IA might represent changes in the cell surface glycolipid and glycoprotein and express a kind of functional dedifferentiations of the bladder tumors. Therefore, the morphological analysis using scanning immunoelectron microscopy might be valuable for the analysis of the variety and the growth pattern of human bladder tumors.