Changes of Lexand Dimeric LexHaptens and their Sialylated Antigens During Development of Human Kidney and Kidney Tumors

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Abstract
The carbohydrate antigen termed Lex (Gal.beta.1 .fwdarw. 4[Fuc.alpha.l .fwdarw. 3]GlcNAc.beta.1 .fwdarw. R), its di- or trimeric form, and their sialylated antigens have been characterized as developmentally regulated, tumor-associated antigens in human gastrointestinal epithelia. In this paper, remarkable changes of these antigens, defined by respective monoclonal antibodies FH3, FH4, and FH6, in fetal kidney (mesonephros and metanephros) and other urogenital organs, as well as in various types of kidney tumors, have been investigated. During the development of each organ and tissue, the antigens were found to be maximally expressed at a defined period of organogenesis, and a shifting of expression from one locus to another was observed. Each antigen showed a slightly but clearly different stage of maximum expression. The following changes in metanephros development are of particular interest. Expression of the antigen defined by FH3 followed by the antigen defined by FH4 appeared only after six weeks of gestation in the convoluted tubuli at the central region of metanephros, and propagated rapidly into those at the peripheral cortex region with a simultaneous regression at the central region. The regression of FH4 antigen was more rapid than that of FH3. All three antigens were expressed in the medullar thin tubuli, which develop into the thin-limb of Henle''s loop, in which only the antigens defined by FH3 and FH4 persisted and FH6 antigen disappeared. Well-differentiated, but not undifferentiated, renal adenocarcinomas strongly expressed the antigens defined by FH4 and FH6, although the antigen defined by FH6 was expressed in more differentiated tumor cells than the antigen defined by FH4. Well-differentiated cells organized into tubular structures showed a strong expression of these differentiation antigens. However, some tumor cells that were organized into tubular structures, but were characterized by undifferentiated cytomorphology (larger nucleus and smaller volume of cytoplasm), did not express FH4 and FH6 antigens. Thus, cytodifferentiation and histotypic differentiation proceed independently within kidney tumors. The fucosylated type 2 chain structures defined by these three monoclonal antibodies are useful markers that indicate the degree of tumor differentiation.