Quantitative electron microscopy has been used to examine the correlation between numbers of desmo-somes and the histopathological grade and stage of papillary transitional cell carcinomas in human urinary bladder. Numbers of desmosomes (desmosomal density) per 100 pm of cell perimeter were quan-titated in 6 examples of normal epithelium, 11 noninvasive papillary transitional cell carcinomas, 8 in-vasive transitional cell carcinomas arising from papillary lesions, 3 invasive transitional cell carcinomas which had prominent foci of glandular and squamous differentiation, and 1 squamous cell carcinoma. Desmosomal densities were increased in noninvasive transitional cell carcinomas, as compared with normal epithelium, but decreased in invasive transitional cell carcinomas. However, in areas of glandular or squamous differentiation in invasive tumors, desmosomal densities were increased, possibly reflecting the changes in cell phenotype. The decrease in numbers of desmosomes in invasive transitional cell carcinomas may contribute to reductions in cell adhesiveness. Cancer 47:104-112, 1981. ESMOSOMES ARE INTERCELLULARjUnCtiOIlS which D provide sites of strong adhesion between epithe-lial cell^.^^^^^^^^ In many carcinomas, intercellular adhesion is Although intercellular adhesion is a multifactorial process, deficiencies in inter-cellular junctions may be a particularly important contributing factor to such decreases in intercellular adhesion.31 It has been proposed that decreased inter-cellular adhesion may explain certain patterns of tumor and may be a prerequisite for stromal invasion and metastasis.2i Although the validity of these concepts concerning tumor aggressiveness remains an open question,26 decreased cell adhesion is likely to contribute to the increased sloughing of cells, which is observed in association with some urinary bladder car-cinomas and is of practical importance in diagnostic cytopathology. Ultrastructural studies have demonstrated abnormalities in intercellular junctions in urinary bladder carcinomas in h ~ m a n s ~ ~ J ~ and in animals. i 2 3 3 2 6 * 2 7 Recently , quantitative electron microscopy studies on chemical carcinogen-induced urinary bladder transitional cell carcinomas in Fischer rats have shown that numbers of desmosomes are significantly different in preinvasive and invasive epithelial tumors.26 Comparable quantitative electron microscopy studies have not been reported for human bladder tumors. A problem in drawing analogies between the rat model for chemical carcinogen-induced bladder carci-noma and human bladder carcinoma arises from the fact that, in the rat model, progressive squamous cell differentiation occurs during tumorigenesis, whereas, in humans, transitional cell differentiation often persists throughout the clinical course. Typically, in the rat an admixture of malignant transitional cells and squa-mous cells is present by the time carcinomas become i n ~ a s i v e. ~ ~ Since cell phenotype per se can influence both desmosomal ultrastructure and numbers,1~s~26 the ...